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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 English | WPRIM | ID: wpr-887717

ABSTRACT

Objective@#To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells.@*Methods@#Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1).@*Results@#High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.@*Conclusion@#The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis , Carcinoma, Ovarian Epithelial/metabolism , Cell Line, Tumor , Cofilin 1/metabolism , Drug Resistance, Neoplasm , Female , Humans , Ovarian Neoplasms/metabolism , Paclitaxel/therapeutic use , Phosphoprotein Phosphatases/metabolism , Phosphorylation
5.
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
6.
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
7.
Article in Chinese | WPRIM | ID: wpr-828405

ABSTRACT

The tirucallane-type triterpenoids, composed of six isoprene units, belong to a group of tetracyclic triterpenoids. Although the naturally-derived tirucallane-type triterpenoids were found in a small amount, the kind of compounds showed various structures, which consist of apo-type, linear said-chain-type and cyclolike said-chain-type and broad bioactivities, such as cytotoxicity, anti-inflammation, antioxidation and anti-plasmin, etc. This paper summarized origins, structures and bioactivities of tirucallane-type triterpenoids in recent ten years. The future research and exploration of tirucallane-type triterpenoids were discussed and prospected.


Subject(s)
Antineoplastic Agents, Phytogenic , Molecular Structure , Triterpenes
8.
Braz. j. med. biol. res ; 52(11): e8657, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039263

ABSTRACT

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.


Subject(s)
Humans , Female , Breast Neoplasms/metabolism , Paclitaxel/metabolism , HMGB1 Protein/metabolism , MicroRNAs/metabolism , MCF-7 Cells/metabolism , Antineoplastic Agents, Phytogenic/metabolism , Autophagy/genetics , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic/genetics , Up-Regulation/genetics , Paclitaxel/therapeutic use , Apoptosis/genetics , Drug Resistance, Neoplasm/genetics , HMGB1 Protein/genetics , MicroRNAs/genetics , Antineoplastic Agents, Phytogenic/therapeutic use
9.
Acta cir. bras ; 34(3): e201900305, 2019. graf
Article in English | LILACS | ID: biblio-989062

ABSTRACT

Abstract Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.


Subject(s)
Animals , Male , Rats , Stomach Neoplasms/drug therapy , Plant Extracts/therapeutic use , Adenocarcinoma/drug therapy , Usnea/chemistry , Acetates/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Rats, Wistar , Neoplasms, Experimental/drug therapy
10.
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
11.
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
12.
Article in English | WPRIM | ID: wpr-776905

ABSTRACT

While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Therapeutic Uses , Apoptosis , Cysteine , Chemistry , Pharmacology , Therapeutic Uses , Disease Models, Animal , Garlic , Chemistry , Humans , Molecular Structure , Neoplasms , Drug Therapy , Metabolism , Signal Transduction
13.
Article in Chinese | WPRIM | ID: wpr-774537

ABSTRACT

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.


Subject(s)
Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Biflavonoids , Pharmacology , Carcinoma, Hepatocellular , Drug Therapy , Pathology , Cell Movement , Cell Proliferation , Dracaena , Chemistry , Hep G2 Cells , Humans , Liver Neoplasms , Drug Therapy , Pathology , Phytochemicals , Pharmacology
14.
Article in English | WPRIM | ID: wpr-776884

ABSTRACT

Eight new annonaceous acetogenins, squamotin A-D (1-4), annosquatin IV-V (5 and 6), muricin O (7) and squamosten B (8), together with four known ones (9-12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1-9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.


Subject(s)
Acetogenins , Chemistry , Pharmacology , Toxicity , Annona , Chemistry , Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Toxicity , Cell Line, Tumor , Cell Survival , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Plant Extracts , Chemistry , Pharmacology , Toxicity , Seeds , Chemistry
15.
Article in Chinese | WPRIM | ID: wpr-772103

ABSTRACT

OBJECTIVE@#To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells.@*METHODS@#The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts.@*RESULTS@#MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice.@*CONCLUSIONS@#The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.


Subject(s)
Acetates , Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Pathology , Cell Line, Tumor , Cell Proliferation , Heterografts , Humans , Lung Neoplasms , Pathology , Methanol , Mice , Mice, Nude , Plant Extracts , Pharmacology
16.
Article in Chinese | WPRIM | ID: wpr-772092

ABSTRACT

OBJECTIVE@#To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model.@*METHODS@#Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay.@*RESULTS@#Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01).@*CONCLUSIONS@# decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Carcinoma, Hepatocellular , Drug Therapy , Allergy and Immunology , Metabolism , Pathology , Drugs, Chinese Herbal , Pharmacology , Kidney , Liver , Pathology , Liver Neoplasms , Drug Therapy , Allergy and Immunology , Metabolism , Pathology , Mice , Necrosis , Neoplasm Proteins , Metabolism , Random Allocation , Up-Regulation
17.
Article in Chinese | WPRIM | ID: wpr-773705

ABSTRACT

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.


Subject(s)
Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Autophagy , Cell Cycle Checkpoints , Diterpenes , Pharmacology , Epoxy Compounds , Pharmacology , Humans , Neoplasms , Drug Therapy , Phenanthrenes , Pharmacology , Tripterygium , Chemistry
18.
Article in English | WPRIM | ID: wpr-773441

ABSTRACT

OBJECTIVE@#This research aimed to evaluate the protective effects of bioactive compounds such as phenolic acids, flavonoids, and tannins present in four species extracted with methanol.@*METHODS@#The total phenolic content of the methanolic extracts was measured spectrophotometrically. The effect of the extracts on cell viability in U266 cells was measured. The effects of extracts on free radical scavenging were assessed by the DPPH test and FRAP assay. Antibacterial effects of the natural products in this report were investigated by using the disc diffusion method.@*RESULTS@#Our results clearly demonstrated that the methanolic extracts were characterized by a high amount of phenolic compounds. It has been speculated that ME-TA and ME-TAl exhibit a significant (P < 0.05) and dose-dependent antiradical potential. The exposure of cells to high doses of extracts almost completely suppressed cell growth in vitro. ME-TA and ME-TAl showed significant cytotoxic effects at a concentration of 100 μg/mL in the U266 cell line. ME-TAl and ME-CF inhibited the growth of B. subtilis and S. aureus, respectively, to the same extent as 10 μg/μL of chloramphenicol at a concentration of 1 mg/mL.@*CONCLUSION@#Overall, these results suggest that plants used in traditional medicine have a novel application as free radical scavengers, bacterial inhibitors and tumor suppressors.


Subject(s)
Anti-Bacterial Agents , Pharmacology , Antineoplastic Agents, Phytogenic , Pharmacology , Antioxidants , Pharmacology , Bacteria , Biological Products , Pharmacology , Cell Line, Tumor , Cell Survival , Humans , Magnoliopsida , Chemistry , Multiple Myeloma , Phytochemicals , Pharmacology , Plant Extracts , Chemistry , Pharmacology
19.
Article in Chinese | WPRIM | ID: wpr-773126

ABSTRACT

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line, Tumor , Drug Carriers , Hydrogen-Ion Concentration , Lipoproteins , Mice , Mice, Nude , Nanoparticles , Neoplasms, Experimental , Drug Therapy , Paclitaxel , Pharmacology
20.
Article in Chinese | WPRIM | ID: wpr-773122

ABSTRACT

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.


Subject(s)
Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line, Tumor , Clausena , Chemistry , Doxorubicin , Humans , Phytochemicals , Pharmacology , Plant Leaves , Chemistry , Plant Stems , Chemistry
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