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1.
Braz. j. med. biol. res ; 54(10): e10891, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285652

ABSTRACT

Juniperus communis (JCo) is a well-known traditional Chinese medicinal plant that has been used to treat wounds, fever, swelling, and rheumatism. However, the mechanism underlying the anticancer effect of JCo extract on colorectal cancer (CRC) has not yet been elucidated. This study investigated the anticancer effects of JCo extract in vitro and in vivo as well as the precise molecular mechanisms. Cell viability was evaluated using the MTT assay. Cell cycle distribution was examined by flow cytometry analysis, and cell apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein expression was analyzed using western blotting. The in vivo activity of the JCo extract was evaluated using a xenograft BALB/c mouse model. The tumors and organs were examined through hematoxylin-eosin (HE) staining and immunohistochemistry. The results showed that JCo extract exhibited higher cytotoxicity against CRC cells than against normal cells and showed synergistic effects when combined with 5-fluorouracil. JCo extract induced cell cycle arrest at the G0/G1 phase via regulation of p53/p21 and CDK4/cyclin D1 and induced cell apoptosis via the extrinsic (FasL/Fas/caspase-8) and intrinsic (Bax/Bcl-2/caspase-9) apoptotic pathways. In vivo studies revealed that JCo extract suppressed tumor growth through the inhibition of proliferation and induction of apoptosis. In addition, there was no obvious change in body weight or histological morphology of normal organs after treatment. JCo extract suppressed CRC progression by inducing cell cycle arrest and apoptosis in vitro and in vivo, suggesting the potential application of JCo extract in the treatment of CRC.


Subject(s)
Animals , Rabbits , Colorectal Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Juniperus , Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Cell Cycle , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Cycle Checkpoints , Mice, Inbred BALB C
2.
Braz. arch. biol. technol ; 64: e21200163, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153296

ABSTRACT

HIGHLIGHTS Isolate, fractionate and characterize extracts obtained from soursop leaves. Use of emerging green technologies such as microwave-ultrasound hybridization. The extracts contain kaempferol, procyanidins, catechin, and quercetin. The total ethanolic extract demonstrates cytotoxic effect on HeLa cells.


Abstract Cervical cancer is classified as the fourth most common malignancy in women. Natural compounds are a therapeutic alternative in cancer therapy. The aim of the study is to isolate, fractionate, and characterize extracts obtained from soursop leaves (Annona muricata L.) and determine their cytotoxic effect against HeLa cervical cancer cells and non-carcinogenic fibroblast 3T3 cells. The phytochemicals of soursop leaves were extracted through emerging green technologies such as the novel use of microwave-ultrasound hybridization and the use of environmentally friendly solvents (water and ethanol), in addition to the purification of extracts enriched in polyphenols by liquid chromatography with Amberlite XAD-16. Total aqueous and ethanolic extract were purified, as well as the fraction one of each extract. The extracts recovered from soursop leaves contained kaempferol and its isomers, procyanidins, catechin, and quercetin. The viability of the cells was determined with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. HeLa and 3T3 cells were exposed to concentrations of 25, 50, 75, 100, 150, 200, and 250 ppm of a solution of soursop leaf extract powder. The MTT assay showed that soursop leaf extracts were toxic to both cell lines in general, however, the ethanolic extract at 25 and 50 ppm demonstrated inhibition in cell viability against the HeLa cancer line and low cytotoxicity for 3T3 fibroblast cells. In conclusion, the novel microwave-ultrasound hybridization technology allows the extraction of polyphenols that may have a potential cytotoxic effect on cancer cells.


Subject(s)
Humans , Female , HeLa Cells , Annona/chemistry , Polyphenols/isolation & purification , Phytochemicals/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Plant Extracts/pharmacology , Catechin/chemistry , Chromatography, Liquid/methods , Ethanol , Antineoplastic Agents, Phytogenic/pharmacology
3.
Article in English | WPRIM | ID: wpr-888781

ABSTRACT

In this study, three new germacranolide sesquiterpenes (1-3), together with six related known analogues (4-9) were isolated from the whole plant of Carpesium cernuum. Their structures were established by a combination of extensive NMR spectroscopic analysis, HR-ESIMS data, and ECD calculations. The anti-leukemia activities of all compounds towards three cell lines (HEL, KG-1a, and K562) were evaluated in vitro. Compounds 1-3 exhibited moderate cytotoxicity with IC


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Asteraceae/chemistry , Drug Screening Assays, Antitumor , Humans , K562 Cells , Phytochemicals/pharmacology , Sesquiterpenes, Germacrane/pharmacology
4.
Article in Chinese | WPRIM | ID: wpr-879151

ABSTRACT

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Carriers , Female , Folic Acid , Glycolates , HeLa Cells , Humans , Micelles , Paclitaxel , Particle Size , Uterine Cervical Neoplasms/drug therapy
5.
Article in English | WPRIM | ID: wpr-881034

ABSTRACT

Paclitaxel, a tetracyclic diterpenoid compounds, was firstly isolated from the bark of the Pacific yew trees. Currently, as a low toxicity, high efficiency, and broad-spectrum natural anti-cancer drug, paclitaxel has been widely used against ovarian cancer, breast cancer, uterine cancer, and other cancers. As the matter of fact, natural paclitaxel from Taxus species has been proved to be environmentally unsustainable and economically unfeasible. For this reason, researchers from all over the world are devoted to searching for new ways of obtaining paclitaxel. At present, other methods, including artificial cultivation of Taxus plants, microbial fermentation, chemical synthesis, tissue and cell culture have been sought and developed subsequently. Meanwhile, the biosynthesis of paclitaxel is also an extremely attractive method. Unlike other anti-cancer drugs, paclitaxel has its unique anti-cancer mechanisms. Here, the source, production, and anti-cancer mechanisms of paclitaxel were summarized and reviewed, which can provide theoretical basis and reference for further research on the production, anti-cancer mechanisms and utilization of paclitaxel.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Humans , Neoplasms/drug therapy , Paclitaxel/pharmacology
6.
Biol. Res ; 52: 1, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011405

ABSTRACT

BACKGROUND: Ethnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum. METHODS: The column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P barbatum, the isolated compounds (1-3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity. RESULTS: Three dihydrobenzofuran derivatives (1-3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3 S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 µM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1,13.4 ± 1.1 and 57.7 ± 0.3 µM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS). CONCLUSION: Based on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.


Subject(s)
Humans , Benzofurans/pharmacology , Carcinoma, Squamous Cell/drug therapy , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Polygonum/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Benzofurans/isolation & purification , Benzofurans/chemistry , Carcinoma, Squamous Cell/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Polygonum/classification , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/isolation & purification
7.
Biol. Res ; 52: 34, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019499

ABSTRACT

BACKGROUND: Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. RESULTS: Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn't inhibit the psoralen-induced ER stress in SMMC7721 cells. CONCLUSIONS: Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma.


Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Endoplasmic Reticulum Stress/drug effects , Ficusin/pharmacology , Liver Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Signal Transduction/drug effects , Protein-Serine-Threonine Kinases/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Ficusin/therapeutic use , Ficusin/chemistry , Liver Neoplasms/pathology
8.
Braz. j. med. biol. res ; 51(7): e7256, 2018. graf
Article in English | LILACS | ID: biblio-951731

ABSTRACT

Cuscuta chinensis polysaccharide (CPS) was extracted using hot water and enzymatically hydrolyzed C. chinensis polysaccharide (ECPS) was produced by the mannase enzymatic hydrolysis process. The purpose of this research was to investigate the antimelanogenic activity of ECPS and CPS in B16F10 melanoma cells. The in vitro antioxidant activity was assessed by their ferric iron reducing power and DPPH free radical scavenging activities. The molecular mass distribution of polysaccharides was determined using SEC-MALLS-RI. CPS was successfully enzymatically degraded using mannase and the weighted average molecular weights of CPS and ECPS were 434.6 kDa and 211.7 kDa. The results of biological activity assays suggested that the enzymatically hydrolyzed polysaccharide had superior antimelanogenic activity and antioxidant effect than the original polysaccharide. ECPS exhibited antimelanogenic activity by down-regulating the expression of tyrosinase, MITF, and TRP-1 without cytotoxic effects in B16F10 melanoma cells. In conclusion, ECPS have the potential to become a skin whitening product.


Subject(s)
Animals , Polysaccharides/pharmacology , Melanoma, Experimental/pathology , Plant Extracts/pharmacology , Cuscuta/chemistry , Melanocytes/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Polysaccharides/isolation & purification , Polysaccharides/chemistry , Seeds/chemistry , Plant Extracts/chemistry , Cell Line, Tumor , Hydrolysis , Antioxidants/isolation & purification , Antioxidants/chemistry
9.
Braz. j. med. biol. res ; 51(10): e7151, 2018. graf
Article in English | LILACS | ID: biblio-951709

ABSTRACT

Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.


Subject(s)
Humans , Flavonoids/pharmacology , Cell Movement/drug effects , Tumor Suppressor Protein p53/drug effects , Apoptosis/drug effects , Colonic Neoplasms/pathology , Cell Proliferation/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Blotting, Western , Tumor Suppressor Protein p53/metabolism , Colonic Neoplasms/metabolism , RNA, Small Interfering , HCT116 Cells , Real-Time Polymerase Chain Reaction
10.
Braz. j. med. biol. res ; 51(4): e6069, 2018. tab, graf
Article in English | LILACS | ID: biblio-889062

ABSTRACT

Melon (Cucumis melo L.) has high economic value and in recent years, its production has increased; however, part of the fruit is wasted. Usually, inedible parts such as peel and seeds are discarded during processing and consumption. Extracts of melon residues were prepared and their phenolic compounds, antioxidants and antiproliferative activities were evaluated. Total phenolic compounds were found in hydroethanolic, hydromethanolic, and aqueous extracts, especially for melon peel (1.016 mg gallic acid equivalent/100 g). Flavonoids total content found for melon peel aqueous extract was 262 µg of catechin equivalent (CA)/100 g. In all extracts of melon peel significant amounts of gallic acid, catechin, and eugenol were found. For total antioxidant capacity, reported as ascorbic acid equivalent, the hydroethanolic and hydromethanolic extracts in peels and hydromethanolic in seeds were 89, 74, and 83 mg/g, respectively. Different extracts of melon showed iron and copper ions chelating activity at different concentrations, especially melon peel aqueous extract, reaching values of 61% for iron and 84% for copper. The hydroethanolic extract of melon peel presented a significant ability for hydroxyl radicals scavenging (68%). To assess the antiproliferative potential in human cancer cell lines, such as kidney carcinoma, colorectal carcinoma, cervical adenocarcinoma and cervical carcinoma, MTT assay was performed. The proliferation was inhibited by 20-85% at extracts concentrations of 0.1-1.0 mg/mL in all cancer cell lines. The results suggest that melon residues extracts display a high antioxidant activity in in vitro assays and have effective biological activity against the growth of human tumor cells.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Cell Proliferation/drug effects , Cucurbitaceae/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Cell Line, Tumor , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Flavonoids/isolation & purification , Flavonoids/pharmacology , Phenols/isolation & purification , Phenols/pharmacology , Seeds/chemistry , Tannins/isolation & purification , Tannins/pharmacology
11.
Braz. j. med. biol. res ; 51(4): e6891, 2018. graf
Article in English | LILACS | ID: biblio-889070

ABSTRACT

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Camellia sinensis/chemistry , Gallbladder Neoplasms/pathology , Polyphenols/pharmacology , S Phase/drug effects , Tea/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gallbladder Neoplasms/drug therapy , Heterografts , Polyphenols/isolation & purification
12.
Medicina (B.Aires) ; 77(4): 283-290, ago. 2017. ilus, graf, tab
Article in English | LILACS | ID: biblio-894480

ABSTRACT

Higher plants have provided various natural derived drugs used currently in western medicine. Tessaria absinthioides (Hook. & Arn.) DC, Asteraceae, is a native plant from South-America with reported ethnopharmacological and culinary uses. Despite recent scientific reports about plants properties, there is not a well conducted research about its anticancer and potential toxic effects. The current work demonstrates the plant aqueous extract composition; the in vitro induced cytotoxicity, and explores, in vivo, its oral toxicity and antitumoral effects. Composition of aqueous extract was determined by phytochemical reactions. Cytotoxicity was tested in tumoral (Hela, Gli-37, HCT-116 and MCF-7) and non-tumoral (HBL-100) cells, using MTT assay. Oral toxicity and the antitumor activity against colorectal carcinoma were studied in rodents. The chemical analysis revealed the presence of flavonoids, carbohydrates, sterols, terpenes and tannins. Cytotoxicity towards tumoral cells was observed (CV50: 3.0 to 14.8 μg/ml); while in non-tumoral cells, extracts evidenced a selective reduced toxicity (CV50: 29.5 μg/ml). Oral administration of the extract does not induce acute nor dose-repeated toxicity at doses up to 2000 mg/kg and 1000 mg/kg/day, respectively. The antitumoral effect was confirmed by a significant increase in a median survival from 24 weeks (non-treated) to 30 weeks (T. absinthioides treated). The present data indicate that T. absinthioides extract exhibits cytotoxicity against cancer cell lines, with no-toxic effects and significant antitumoral effects in colorectal cancer when is orally administrated. In conclusion, T. absinthioides possesses selective cytotoxicity and antitumoral activities, making its plant derivatives products promising for cancer research and treatment.


Las plantas superiores han provisto numerosos derivados naturales usados actualmente por la medicina occidental. Tessaria absinthioides (Hook & Arn) DC, Asteraceae, es una planta autóctona de Sudamérica con informes de uso etnofarmacológico y culinario. A pesar de los reportes científicos sobre las propiedades de esta planta, no existen estudios que caractericen sus efectos antitumorales ni sus efectos tóxicos. En el presente trabajo se describe la composición del extracto acuoso de T. absinthioides, sus propiedades citotóxicas in vitro, y explora in vivo la toxicidad oral y su capacidad de afectar la progresión de tumores. La composición se determinó mediante reacciones fitoquímicas. La citotoxicidad se estudió en líneas celulares tumorales (Gli-37, HeLa, HCT-116 y MCF-7) y no tumorales (HBL-100), utilizando el ensayo de MTT. La toxicidad oral de los extractos y su capacidad antitumoral sobre carcinoma colorrectal se analizaron en roedores. El análisis del extracto acuoso evidenció flavonoides, carbohidratos, esteroles, terpenos y taninos. La citotoxicidad sobre células tumorales resultó similar a la observada para el 5-fluoracilo (CV50: 3.0 a 14.8 μg/ml); mientras que, en células no tumorales, el efecto estuvo selectivamente reducido (CV50: 29.5 μg/ml). La administración oral del extracto no indujo toxicidad aguda ni a dosis repetidas (dosis hasta 2000 mg/kg y 1000 mg/kg/día, respectivamente). Los efectos antitumorales se confirmaron mediante un significativo aumento de la supervivencia en el grupo tratado con T. absinthioides. En conclusión, de acuerdo a los resultados obtenidos, T. absinthioides y sus derivados naturales representan un campo prometedor de estudio para la investigación en el tratamiento del cáncer.


Subject(s)
Animals , Rabbits , Rats , Plant Extracts/pharmacology , Colorectal Neoplasms/drug therapy , Asteraceae/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Tetrazolium Salts , Plant Extracts/therapeutic use , Colorectal Neoplasms/pathology , Rats, Sprague-Dawley , Toxicity Tests , Cell Line, Tumor , Disease Models, Animal , Fluorouracil , Mice, Inbred BALB C , Antineoplastic Agents, Phytogenic/therapeutic use
13.
Bol. latinoam. Caribe plantas med. aromát ; 16(2): 99-109, mar. 2017. ilus, tab
Article in English | LILACS | ID: biblio-881373

ABSTRACT

The genus Casearia (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 200 species. In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro; including Casearia arborea (Rich.) Urb. Essential oil was obtained from the fresh leaves by hydrodistillation and analyzed by GC-MS and GC-FID. The cytotoxic effect was determined by WST-1 assay. Chemical analysis of the essential oil revealed a very diversified (n = 37 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (90.2%). These sesquiterpenes included byciclogermacrene (18.7%), germacrene D (12.1%) and α-humulene (11.5%). In addition, the essential oil demonstrated cytotoxic effects against A549 tumor cells in the concentration of 4 µg/mL (EC50) (p < 0.05).


El género Casearia (Salicáceas) se encuentra en las regiones tropicales y sub-tropicales del planeta y comprende alrededor de 200 especies. En Brasil existen 48 especies, 12 de las cuales fueron registradas en el Estado de Río de Janeiro incluyendo Casearia arborea (Rich.) Urb. El aceite esencial fue extraído de hojas frescas por hidrodestilación y analizado por GC-MS y GC-FID. El efecto citotóxico fue determinado por ensayo WST-1. Las cavidades secretorias fueron ocasionalmente encontradas tanto en la lámina foliar como en el pecíolo. El análisis químico del aceite esencial reveló una muy diversa fracción volátil (n = 37 compuestos) formada principalmente por sesquiterpenos no oxigenados (90,2%). Estos sesquiterpenos incluyen biciclogermacreno (18,7%), germacreno D (12,1%) y α-humuleno (11,5%). Además, el aceite esencial demostró efectos citotóxicos contra las células tumorales A549 en una concentración de 4µg/mL (EC50) (p < 0.05).


Subject(s)
Casearia/chemistry , Cytotoxins/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Plant Leaves/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chromatography, Gas/methods , Salicaceae/chemistry , Sesquiterpenes/analysis
14.
Cell Journal [Yakhteh]. 2017; 19 (1): 94-101
in English | IMEMR | ID: emr-185796

ABSTRACT

Objective: Crocin [Cro] and crocetin [Crt] are two widely known saffron carotenoids, which exert anticancer effects by different mechanisms. Here, we investigated and compared the preventive effect of Cro and Crt at the initiation and promotion stages of breast cancer induction in an animal model


Materials and Methods: In this experimental study, female Wistar albino rats were injected with three doses of N-methyl-N-nitrosourea [NMU]. The preventive intervention was done at different times for the initiation and promotion stages. Thus, Cro/Crt was administered by gavage 20 days before, or one week after, the first NMU injection, for the prevention at the initiation or promotion stages respectively. The treatment was repeated every three days, and continued up to the end of experiment. Tumor appearance was checked by palpation and some parameters were determined after sacrifice


Results: Tumor volume, latency period, and tumor number were significantly decreased in the rat groups treated with both saffron carotenoids for prevention at both the initiation and promotion stages. Tumor incidence was 77% due to NMU injection, which was decreased to 45 and 33% [on average] after Cro and Crt administration, respectively. In addition, enkephaline degrading aminopeptidase [EDA] was decreased significantly in the ovaries of the animals, however, changes in the brain were not significant


Conclusion: Crt/Cro showed a significant protective effect against the NMU-induced breast cancer in rats. However, Crt was more effective than Cro and prevention at the initiation stage was more effective than at the promotion stage


Subject(s)
Animals, Laboratory , Female , Carotenoids/therapeutic use , Anticarcinogenic Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Methylnitrosourea , Rats, Wistar , Disease Models, Animal
15.
Int. j. morphol ; 34(4): 1197-1202, Dec. 2016. ilus
Article in English | LILACS | ID: biblio-840866

ABSTRACT

Cancer has been considered as a stem cell disease. Suspension culture combined with anti-cancer drugs has recently been proposed for isolation of cancer stem cells (CSCs). In the current study, Vincristine as an anti-cancer drug combined with suspension culture was used for isolation and purification of CSCs from human breast cancer cell line (MDA-MB231). The cells were treated with different concentrations of vincristine (0, 2, 4, 6 and 8 ng/ml). Stem cells were identified with the expression of OCT4, nanog, SOX2 and nucleostemin genes by RT-PCR. Mammosphere forming unit was measured upon suspension culture containing EGF, bFGF, LIF, B27, insulin and BSA. The isolated mammospheres were investigated for CD44 expression. Results showed that 4 ng/ml of vincristine for 72 hours could be utilized as the best and most reliable dose which eliminates around 80 % of non-cancer stem cells with no destructive effect on CSCs' viability (P> 0.05). RT-PCR demonstrated that drug treated cells expressed OCT4, nanog, SOX2 and nucleostemin. Mammosphere formation unit of cells pretreated with vincristine was significantly higher than unpretreated ones (P>0.05). Immunofluorescence staining for CD44 depicted high expression of CSC marker among the isolated mammospheres. Vincristine combined with suspension culture can be considered as an appropriate method to isolate CSC.


El cáncer ha sido considerado como una enfermedad de células madre. Recientemente se ha propuesto cultivo en suspensión en combinación con medicamentos contra el cáncer para aislamiento de las células madre del cáncer (CMC). En este estudio se utilizó la vincristina como fármaco anticanceroso combinado con cultivo en suspensión para el aislamiento y purificación de las células madre cancerosas, de la línea celular de cáncer de mama humano (MDA-MB231). Las células se trataron con diferentes concentraciones de vincristina (0, 2, 4, 6 y 8 ng/ml). Las células madre se identificaron mediante la expresión de los genes OCT4, Nanog, SOX2 y nucleostemin por RT-PCR. La unidad de formación mammosphere se midió a través de cultivo en suspensión que contenía EGF, bFGF, LIF, B27, insulina y BSA. Los mammospheres aislados fueron estudiados para la expresión de CD44. Los resultados mostraron que 4 ng/ml de vincristina durante 72 horas podrían ser utilizados como la mejor y más fiable dosis que permite eliminar alrededor del 80 % de las células madre no cancerosas, sin causar un efecto destructivo sobre la viabilidad de las CMC (P> 0,05). La RT-PCR mostró que en las células tratadas con él fármaco hubo expresión de los genes OCT4, Nanog, SOX2 y nucleostemin. La unidad de formación de las células pretratadas con vincristina fue significativamente más alta que las unidades sin tratamiento previo (P>0,05). La inmunofluorescencia para CD44 muestró una alta expresión del marcador de CMC entre mammospheres aisladas. La vincristina en combinación con el cultivo en suspensión puede ser considerado como un método apropiado para aislar CMC.


Subject(s)
Humans , Female , Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/pathology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Vincristine/pharmacology , Hyaluronan Receptors/metabolism , Cell Line, Tumor , Fluorescent Antibody Technique, Indirect , Nanog Homeobox Protein , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Staining and Labeling , Tumor Stem Cell Assay
16.
Biol. Res ; 49: 1-6, 2016. ilus, graf, tab
Article in English | LILACS | ID: biblio-950848

ABSTRACT

CONTEXT: Trichosanthin produced in the root tube of Trichosanthes kirilowii shows anti-tumor activity on a series of cancer cells including Hela, MCF-7, HL-60. But there is little information about its effect on the carcinogenesis of prostate cancer. OBJECTIVE: This work was designed to study the role of trichosanthin on prostate cancer cells PC3. MATERIALS AND METHODS: Trichosanthin was expressed in BL21 strain and purified by affinity chromatography. MTT assay was designed to determine the effect of trichosanthin on growth of PC3 cells at doses of 10, 20, 40, 60, 80, and 120 µg/ml.Then the effect of 50 µg/ml rTCS alone or combined with 2 µM IL-2 on PC3 cell proliferation was analyzed. And the mechanism of rTCS was studied by western blot. After that the in vivo effect of rTCS combined with IL-2 was explored in mice bearing PC3 xenograft tumor. RESULTS: Trichosanthin was successfully expressed in BL21 and purified by 100 mM imidazole. It was shown to inhibit proliferation of PC3 cells in a dose-dependent manner with IC50 50.6 µg/ml. When combined with cytokine IL-2, a significant synergic effect was obtained. The inhibition rate on PC3 was around 50 % in combination group while only 35.5 % in single rTCS group at 50 µg/ml. Further, the expression of full length caspase-8 and Bcl-2 decreased significantly while cleaved caspase-8 and Bax were up-regulated, which suggest that caspase-8-mediated apoptosis pathway may be activated by rTCS in PC3 cells. Moreover, our data demonstrated that tumor volume and tumor weight were significantly reduced in rTCS-treated or rTCS/IL-2-treated nude mice bearing PC3 xenograft tumor compared with control. And significant difference was also found between rTCS and rTCS/IL-2 group. CONCLUSIONS: This study demonstrates that rTCS is a potential agent with high in vitro and in vivo anti-tumor activity on PC3 cells. And rTCS combined with IL-2 is a promising strategy in treating patients with prostate cancer in future.


Subject(s)
Animals , Male , Female , Mice , Prostatic Neoplasms/drug therapy , Trichosanthin/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Prostatic Neoplasms/pathology , Tetrazolium Salts , Time Factors , Recombinant Proteins/pharmacology , Blotting, Western , Reproducibility of Results , Apoptosis/drug effects , Cell Line, Tumor , Tumor Burden , Cell Proliferation/drug effects , Formazans
17.
Rev. paul. pediatr ; 33(1): 82-87, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744697

ABSTRACT

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .


OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .


Subject(s)
Animals , Humans , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Macrocyclic Compounds/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Diterpenes/chemistry , Diterpenes/isolation & purification , Euphorbia/chemistry , Molecular Conformation , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/isolation & purification , Phenotype , Structure-Activity Relationship , Tumor Cells, Cultured
18.
Braz. j. biol ; 75(1): 69-76, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744335

ABSTRACT

The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle) cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g–1, respectively) and calyx extracts (474.09 and 148.35 mg g–1, respectively) from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 μg mL–1) and calyces (37.15 μg mL–1) demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562), with IC50 values of 0.12 mg mL–1 (organosuper®) and 1.16 mg mL–1 (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects.


O objetivo deste estudo foi avaliar a atividade antioxidante, antitumoral e o conteúdo de fenólicos e flavonoides do extrato metanólico das folhas e cálices de Hibiscus sabdariffa (rosela) cultivada com cama de frango e organosuper ® em três modos de aplicação. O conteúdo fenólico total de cada extrato foi determinado utilizando o reagente de Folin-Ciocalteu e cloreto de alumínio para flavonoides. Os parâmetros antioxidantes foram avaliados pelo ensaio de seqüestro de radical livre 2, 2-difenil-1-picrilhidrazil (DPPH.). Na avaliação antitumoral utilizou-se o ensaio colorimétrico com sulforrodamina B. Observou-se o maior conteúdo de fenólicos e flavonoides em extratos de folhas (389.98 e 104.52 mg g–1, respectivamente) e extratos de cálice (474.09 e 148.35 mg g–1, respectivamente) de plantas cultivadas com organosuper ®, embora esses valores não diferiram significativamente daqueles observados para os outros tratamentos. O IC50 de folhas (43.48 µg mL–1) e cálices (37.15 µg mL–1) demonstrou que ambos têm substâncias que podem contribuir para a ação seqüestradora de radicais livres. O extrato metanólico dos cálices mostrou seletividade na linhagem de leucemia (K-562), com valores de IC50 de 0,12 mg mL–1 (organosuper®) e 1,16 mg mL–1 (cama-de-frango) com concentração-dependente e efeito citotóxico e citocida.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Cell Proliferation/drug effects , Hibiscus/chemistry , Phenols/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Plant Leaves/chemistry
19.
Mem. Inst. Oswaldo Cruz ; 110(1): 1-22, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741625

ABSTRACT

An increasingly asked question is 'can we confidently link bats with emerging viruses?'. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.


Subject(s)
Animals , Humans , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Fatty Acids/analysis , Industrial Waste/analysis , Malus/chemistry , Plant Oils/isolation & purification , Seeds/chemistry , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/economics , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/adverse effects , Antioxidants/economics , Antioxidants/pharmacology , Cell Line, Tumor , Chemical Phenomena , CHO Cells , Cricetulus , Cell Proliferation/drug effects , Dietary Supplements/adverse effects , Dietary Supplements/economics , Fatty Acids, Nonesterified/adverse effects , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/economics , Fatty Acids/adverse effects , Fatty Acids/economics , Food Preservatives/adverse effects , Food Preservatives/economics , Food Preservatives/isolation & purification , Food Preservatives/pharmacology , Food-Processing Industry/economics , Fruit/chemistry , Fruit/economics , India , Industrial Waste/economics , Linoleic Acid/adverse effects , Linoleic Acid/analysis , Linoleic Acid/economics , Oleic Acid/adverse effects , Oleic Acid/analysis , Oleic Acid/economics , Plant Oils/chemistry , Plant Oils/economics , Plant Oils/pharmacology
20.
Bol. latinoam. Caribe plantas med. aromát ; 14(1): 42-47, ene.2015. tab
Article in Portuguese | LILACS | ID: lil-795832

ABSTRACT

Essential oils from leaves and stems of Eperua duckeana Cowan (Fabaceae) were extracted by hydrodistillation and analyzed by GC/FID and GC/MS. Sixteen and nineteen components were identified by comparison by their retention indices (RI) and mass spectra. The major components identified in leaves were (E)-caryophyllene (31.8 percent), caryophyllene oxide (25.7 percent) and alpha- humulene (4.4 percent), and stems (E)-caryophyllene (34.5 percent) and germacrene D (25.9 percent). The stems oil essential showed high cytotoxicity against tumor cell lines of leukemia (HL-60). This is the first report regarding the essential oil composition and citotoxicy activity of the essential oil of Eperua duckeana Cowan...


Óleos essenciais de folhas e galhos de Eperua duckeana Cowan (Fabaceae) foram extraídos por hidrodestilação e analisados por CG-DIC e CG-EM. Dezesseis e dezenove componentes foram identificados por comparação com seus índices de retenção (IR) e espectros de massas. Os componentes principais identificados nas folhas foram o (E)-cariofileno (31,8 por cento), óxido de cariofileno (25,7 por cento) e o alfa- humuleno (4,4 por cento), nos galhos (E)-cariofileno (34,5 por cento) e o D-germacreno (25,9 por cento). O óleo essencial dos galhos mostrou alta citoxicidade contra linhagens de células de leucemia (HL-60). Esse é a primeiro relato abordando a composição dos óleos essenciais e a atividade citotóxica do óleo essencial de Eperua duckeana Cowan...


Subject(s)
Humans , Oils, Volatile/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Fabaceae/chemistry , Plant Leaves/chemistry , Brazil , Chromatography, Gas , Cell Line, Tumor , Sesquiterpenes/analysis , Plant Stems/chemistry
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