Anticancer activity of Inula graveolens by induction of ROS-independent apoptosis and suppression of IL6-IL8 in cervical cancer cells / Actividad anticancerígena de Inula graveolens por inducción de apoptosis independiente de ROS y supresión de IL6-IL8 en células de cáncer de cuello uterino

Cancer is an important disease that causing to deaths in the world. Cervical cancer is one of the most common among women and must be treated quickly to prevent cell proliferation. Natural products have been used for cancer treatment due to their antiproliferative and apoptosis induction properties. In the present study, we aimed to determine the antiproliferative and apoptosis induction activities of methanol extract of Inula graveolens (IGME) in the human cerival cancer cell line (HeLa). Antiproliferative activity of IGME was evaluated by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) method. Apoptosis induction activity was determined by AnnexinV/propodium iodide staining with FACS. ROS induction was determined by DCFH-DA (2',7'-Dichlorofluorescin diacetate) staining. Interleukin 6 and 8 levels (IL-6 and IL-8) were determined by the Elisa method. IGME exhibited antiproliferative effect and induced apoptosis in the HeLa cells. IL-6, IL-8 and intracellular ROS levels were decreased after treatment of IGME. Consequently, IGME was found to have antiproliferative and apoptosis induction activities as an indicator of the anticancer activity.

El cáncer es una enfermedad importante que causa muertes en el mundo. El cáncer de cuello uterino es uno de los más comunes entre las mujeres y debe tratarse rápidamente para evitarla proliferación celular. Los productos naturales se han utilizado para el tratamiento del cáncer debido a sus propiedades anti proliferativas y de inducción de la apoptosis. En el presente estudio, nuestro objetivo fue determinar las actividades de inducción de apoptosis y antiproliferativas del extracto de metanol de Inula graveolens (IGME) en la línea celular de cáncer de cuello uterino humano (HeLa). La actividad antiproliferativa de IGME se evaluó utilizando el método MTT (bromuro de 3-[4,5-dimetiltiazol-2-il]-2,5-difenil-tetrazolio). La actividad de inducción de apoptosis se determinó mediante tinción con anexina V/yoduro de propodio con FACS. La inducción de ROS se determinó mediante tinción con DCFH-DA (diacetato de 2',7'-diclorofluoresceina). Los niveles de interleucina 6 y 8 (IL-6 e IL-8) se determinaron por el método Elisa. IGME exhibió un efecto antiproliferativo e indujo apoptosis en las células HeLa. Los niveles de IL-6, IL-8 y ROS intracelulares disminuyeron después del tratamiento con IGME. En consecuencia, se encontró que IGME tenía actividades antiproliferativas y de inducción de apoptosis como indicador de la actividad anticancerígena.

Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer.

Polyphenols are a broad group of bioactive phytochemicals with powerful antioxidant, anti-inflammatory, immunomodulatory, and antiviral activities. Numerous studies have demonstrated that polyphenol extracts obtained from natural sources can be used for the prevention and treatment of cancer. Pomegranate peel extract is an excellent source of polyphenols, such as punicalagin, punicalin, ellagic acid, and caffeic acid, among others. These phenolic compounds have antineoplastic activity in in vitro models of cervical cancer through the regulation of cellular redox balance, induction of apoptosis, cell cycle arrest, and modulation of different signaling pathways. The current review summarizes recent data from scientific reports that address the anticancer activity of the predominant polyphenol compounds present in PPE and their different mechanisms of action in cervical cancer models.

Chemopreventive Effect on Human Colon Adenocarcinoma Cells of Styrylquinolines: Synthesis, Cytotoxicity, Proapoptotic Effect and Molecular Docking Analysis.

Seven styrylquinolines were synthesized in this study. Two of these styrylquinolines are new and were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, and normal cells (HaCaT). According to the results, compounds 3a and 3d showed antiproliferative activity in SW480 and SW620 cells, but their effect seemed to be caused by different mechanisms of action. Compound 3a induced apoptosis independent of ROS production, as evidenced by increased levels of caspase 3, and had an immunomodulatory effect, positively regulating the production of different immunological markers in malignant cell lines. In contrast, compound 3d generated a pro-oxidant response and inhibited the growth of cancer cells, probably by another type of cell death other than apoptosis. Molecular docking studies indicated that the most active compound, 3a, could efficiently bind to the proapoptotic human caspases-3 protein, a result that could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. The obtained results suggest that these compounds have chemopreventive potential against CRC, but more studies should be carried out to elucidate the molecular mechanisms of action of each of them in depth.

Explore the antiproliferative phytocompounds from ethanolic extracts of Citrus paradisi against liver cancer cell line by chemical analysis using TLC and FT-IR spectroscopy / Explorar os fitocompostos antiproliferativos de extratos etanólicos de Citrus paradisi contra linhagem de células de câncer de fígado por análise química usando espectroscopia de TLC e FT-IR

The aim of the present study was to evaluate the in vitro antiproliferative activity of ethanolic extract of leaves and fruits Citrus paradisi plant on HepG-2 liver cell lines by MTT (3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2Hterazolium bromide) assay and to isolate and characterize the antiproliferative compounds by TLC (Thin layer chromatography) and FT-IR (Fourier transforms Infrared) spectroscopy. Qualitative phytochemical screening tests were performed to detect phytochemicals compounds from the crude extracts. Antioxidant activity of the plant extracts were characterized by using DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging method. The results showed that antioxidant activity using DPPH were found to be increased in a concentration dependent manner and decreased cell viability and cell growth inhibition in a dose dependent manner. The findings from this study indicated that fruit extract exhibited good antiproliferation and antioxidant potential. The seven functional groups of phytocompounds such as carboxylic acid, amine salt, aromatic compounds, cyclic alkene, aldehyde, fluoro compounds and alkene were detected by FT-IR which indicated that fruit extracts of Citrus paradisi possessed vast potential as a medicinal drug especially in liver cancer treatment.

O objetivo do presente estudo foi avaliar a atividade antiproliferativa in vitro do extrato etanólico de folhas e frutos da planta Citrus paradisi em linhagens de células hepáticas HepG-2 por MTT (3- (4, 5-dimetil-2-tiazolil) -2, Ensaio de brometo de 5-difenil-2H-terazólio) e isolar e caracterizar os compostos antiproliferativos por espectroscopia de TLC (cromatografia de camada fina) e FT-IR (infravermelho com transformadas de Fourier). Testes qualitativos de triagem fitoquímica foram realizados para detectar compostos fitoquímicos nos extratos brutos. A atividade antioxidante dos extratos vegetais foi caracterizada pelo método de eliminação de radicais livres DPPH (2,2-difenil-1-picrilhidrazil). Os resultados mostraram que a atividade antioxidante usando DPPH aumentou de uma maneira dependente da concentração e diminuiu a viabilidade celular e a inibição do crescimento celular de uma maneira dependente da dose. Os resultados deste estudo indicaram que o extrato de fruta exibiu bom potencial antiproliferação e antioxidante. Os sete grupos funcionais de fitocompostos, como ácido carboxílico, sal de amina, compostos aromáticos, alceno cíclico, aldeído, compostos de flúor e alceno, foram detectados por FT-IR, o que indicou que extratos de frutas de Citrus paradisi possuíam vasto potencial como medicamento, especialmente no tratamento de câncer do fígado.

Explore the antiproliferative phytocompounds from ethanolic extracts of Citrus paradisi against liver cancer cell line by chemical analysis using TLC and FT-IR spectroscopy

Abstract The aim of the present study was to evaluate the in vitro antiproliferative activity of ethanolic extract of leaves and fruits Citrus paradisi plant on HepG-2 liver cell lines by MTT (3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-terazolium bromide) assay and to isolate and characterize the antiproliferative compounds by TLC (Thin layer chromatography) and FT-IR (Fourier transforms Infrared) spectroscopy. Qualitative phytochemical screening tests were performed to detect phytochemicals compounds from the crude extracts. Antioxidant activity of the plant extracts were characterized by using DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging method. The results showed that antioxidant activity using DPPH were found to be increased in a concentration dependent manner and decreased cell viability and cell growth inhibition in a dose dependent manner. The findings from this study indicated that fruit extract exhibited good antiproliferation and antioxidant potential. The seven functional groups of phytocompounds such as carboxylic acid, amine salt, aromatic compounds, cyclic alkene, aldehyde, fluoro compounds and alkene were detected by FT-IR which indicated that fruit extracts of Citrus paradisi possessed vast potential as a medicinal drug especially in liver cancer treatment.

Resumo O objetivo do presente estudo foi avaliar a atividade antiproliferativa in vitro do extrato etanólico de folhas e frutos da planta Citrus paradisi em linhagens de células hepáticas HepG-2 por MTT (3- (4, 5-dimetil-2-tiazolil) -2, Ensaio de brometo de 5-difenil-2H-terazólio) e isolar e caracterizar os compostos antiproliferativos por espectroscopia de TLC (cromatografia de camada fina) e FT-IR (infravermelho com transformadas de Fourier). Testes qualitativos de triagem fitoquímica foram realizados para detectar compostos fitoquímicos nos extratos brutos. A atividade antioxidante dos extratos vegetais foi caracterizada pelo método de eliminação de radicais livres DPPH (2,2-difenil-1-picrilhidrazil). Os resultados mostraram que a atividade antioxidante usando DPPH aumentou de uma maneira dependente da concentração e diminuiu a viabilidade celular e a inibição do crescimento celular de uma maneira dependente da dose. Os resultados deste estudo indicaram que o extrato de fruta exibiu bom potencial antiproliferação e antioxidante. Os sete grupos funcionais de fitocompostos, como ácido carboxílico, sal de amina, compostos aromáticos, alceno cíclico, aldeído, compostos de flúor e alceno, foram detectados por FT-IR, o que indicou que extratos de frutas de Citrus paradisi possuíam vasto potencial como medicamento, especialmente no tratamento de câncer do fígado.

Design, Synthesis, and in†vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2-5.4 µM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.

Vochysia tucanorum Mart. butanol fraction presents antitumoral activity in vivo and prevents the installation of cachexia in solid Ehrlich tumor model.

BACKGROUND: Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50-80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian "Cerrado". The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development. METHODS: Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 µl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements. RESULTS: The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed. CONCLUSIONS: The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.

Antimutagenic, Antiproliferative and Antioxidant Properties of Sea Grape Leaf Extract Fractions (Coccoloba uvifera L.).

BACKGROUND: Cancer is a disease characterized by the invasion and uncontrolled growth of cells. One of the best ways to minimize the harmful effects of mutagens is through the use of natural antimutagens. In this regard, the search for new antimutagens that act in the chemoprevention could represent a promising field in this area. OBJECTIVE: In this study biological potential of 11 fractions from Coccoloba uvifera L. leaf hexane extract was evaluated by several in vitro tests. METHODS: Leaves were lyophilized and hexane extraction was performed. The extract was fractionated by column chromatography with hexane, ethyl acetate, and methanol. The antimutagenic (Ames test), antiproliferative (MTT test), and antioxidant capacity (DPPH, ABTS, and ferrous ion chelation) of the fractions were evaluated. RESULTS: Fractions 4, 6, 8, and 9 have antimutagenic activity (against sodium azide in strain TA100), fraction 11 showed antiproliferative capacity (IC50 of 24 ± 9 µg/mL in cells of HCT 116). The fractions with the highest activity were analyzed by HPLC-MS and lupeol, acacetin, and ß-sitosterol were identified. CONCLUSION: This study demonstrates, for the first time, the bioactivity of C. uvifera leaf as a new source of High Biological Value Compounds (HBVC), which can be of interest to the food and pharmaceutical industries.

In vitro anti-proliferative effect and in vivo antitumor action of daphnetin in different tumor cells.

ANTECEDENTES: Los efectos antiinflamatorios de la dafnetina (7,8-dihidroxicumarina) han sido bien documentados, pero su potencial como agente anticanceroso es controversial y no se ha explorado suficientemente. MATERIAL Y MÉTODOS: En este trabajo se evalúa el efecto antiproliferativo in vitro de la dafnetina en tres líneas celulares mediante ensayos de MTT, así como su efecto antitumoral in vivo en cuatro diferentes tipos de tumores en ratones. RESULTADOS: Con una correlación entre los resultados in vitro e in vivo, los tipos de células probadas tienen diferente sensibilidad al compuesto. Las siguientes líneas celulares están ordenadas de acuerdo con la potencia antiproliferativa in vitro de la dafnetina: células de melanoma B16 (IC50 = 54 ± 2.8 µM) > células de adenocarcinoma de mama MXT (IC50 = 74 ± 6.4 µM) > células de carcinoma de colon C26 (IC50 = 108 ± 7.3 µM). In vivo, la dosis antitumoral óptima de dafnetina fue de 40 mg/kg, y las magnitudes de inhibición fueron las siguientes: tumor B16 (48%) > tumor MXT (40%) > tumor fibrosarcoma S180 (30%) > tumor C26 (20%). CONCLUSIÓN: Los resultados indican que la dafnetina podría tener un impacto como adyuvante para mejorar la efectividad de la quimioterapia convencional.

BACKGROUND: The anti-inflammatory effects of daphnetin (7,8-dihidroxicoumarin) have been well-documented, but the potential of daphnetin as an anticancer agent is controversial and remains insufficiently explored. MATERIAL AND METHODS: In this work, we evaluated the in vitro anti-proliferative effect of daphnetin in three cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, as well as its in vivo antitumor effect in four different types of mouse tumor. RESULTS: With a correlation between in vitro and in vivo results, the tested cell types have different sensitivity to the compound. The following cell lines are arranged according to the in vitro anti-proliferative potency of daphnetin: B16 melanoma cells (inhibitory concentrations 50 [IC50] = 54 ± 2.8 µM) > mitoxantrone (MXT) breast adenocarcinoma cells (IC50 = 74 ± 6.4 µM) > C26 colon carcinoma cells (IC50 = 108 ± 7.3 µM). In vivo, the optimal antitumor dose of daphnetin was 40 mg/kg and the magnitudes of inhibition were the following: B16 tumor (48%) > MXT tumor (40%) > S180 fibrosarcoma tumor (30%) > C26 tumor (20%). CONCLUSION: Our results indicate that daphnetin might have an impact as adjuvant to improve the effectiveness of conventional chemotherapy.

Cytotoxicity of sodium selenite in HaCaT cells induces cell death and alters the mRNA expression of PUMA, ATR, and mTOR genes.

BACKGROUND: By identifying the molecular mechanisms underlying sodium selenite (Na2SeO3) cytotoxicity during exposure in non-tumor cells (HaCaT cells), we will improve the current understanding of its antiproliferative effects and modulation of gene expression in the main pathways related to the cell cycle, cell death, oxidative stress, and DNA damage and repair. METHODS: Non-tumor HaCaT cells were treated with Na2SeO3 to induce cytotoxicity, and the effects were investigated using an MTT assay (cell viability), real-time cell analysis (profiling the cell index), flow cytometry (membrane integrity, cell cycle disruption, and apoptosis), a comet assay (genotoxicity, i.e., DNA damage), and RT-qPCR (mRNA expression of genes). RESULTS: Treatment with Na2SeO3 was cytotoxic at 10 µM, producing morphological changes in cells (cytoplasmic granulations); however, it did not have a genotoxic effect. Na2SeO3 induced cell membrane damage, cell death, and cell cycle arrest in HaCaT cells. It also altered the mRNA expression levels of PUMA, ATR, and mTOR genes. However, it had no effect on the mRNA expression of caspases or PARP1, BIRC5, BECN1, and c-MYC genes, suggesting that Na2SeO3 causes PUMA-dependent apoptosis in HaCaT cells. The mRNA expression of specific genes related to oxidative stress, DNA damage and repair, and cell cycle control were unchanged by Na2SeO3. CONCLUSIONS: We demonstrated the cytotoxic effect of Na2SeO3 in HaCaT cells by analyzing mRNA expression patterns, changes in cell morphology, and proliferation kinetics.

Cytotoxic and antiproliferative activities of amphibian (anuran) skin extracts on human acute monocytic leukemia cells.

The use of preparations derived from frog skins for curative purposes antedates research history and is perpetuated in current medicine. The skins of anuran's (frogs and toads) are a rich source of compounds with a great importance in the search of antibiotics, analgesics, immunomodulators, enzymatic inhibitors and antitumoral agents applying to human health. Nowadays, cancer is the second most common cause of mortality with more than 8.2 million of deaths worldwide per year. Acute monocytic leukemia is the subtype M5 of acute myeloid leukemia (AML) a cancer type with reduced survival rates in patients. The monocyte to macrophage differentiation plays an essential role increasing the expansion of AML cell lines. Herein we studied the cytotoxic and antiproliferative activities of eleven amphibian species of three families belonging to Argentinean zones, against THP-1 monocytes and THP-1 macrophages acute monocytic leukemia cell lines. The evaluated species showed pronounced deleterious effects on acute monocytic leukemia THP-1 cell lines, reducing cell proliferation and inducing apoptosis, autophagy and in some cases cell aggregation. Being this work of great importance for the study of new natural anti-cancer compounds.

Flavonoids from the Amazon plant Brosimum acutifolium induce C6 glioma cell line apoptosis by disrupting mitochondrial membrane potential and reducing AKT phosphorylation.

Glioblastoma, which is highly invasive and has a poor patient prognosis, is the most common type of brain tumor. Flavonoids have known antiproliferative and antineoplastic effects, such as apoptosis induction and tumor growth inhibition. We investigated the effects of treatment with three flavonoids (BAS-1, BAS-4, and BAS-6) isolated from the Amazon plant Brosimum acutifolium on the proliferation and migration of the C6 glioma cell line. Cytotoxicity was evaluated by MTT assay, and morphological changes were evaluated by phase-contrast microscopy and by transmission electron microscopy. Apoptosis was determined using Annexin V-FITC-propidium iodide (PI) staining. A hemolysis assay was used to evaluate plasma membrane injury. Antiproliferative effects were assessed by wound migration and colony formation assays. Mitochondrial transmembrane potential (ΔΨm) was determined using JC-1 dye and flow cytometry. To identify the flavonoid targets, western blotting was performed. BAS-1 and BAS-4 reduced C6 cell proliferation in a dose-dependent manner. BAS-6 showed no effect. Due to its high toxicity toward primary glial cells and its high hemolytic index, BAS-1 was not used in the remaining experiments. BAS-4 treatment did not induce cytotoxicity in primary glial cells; however, in glioma cells, it suppressed migration and invasion and led to apoptosis through mitochondrial damage, ΔΨm loss, cell cycle arrest, and reduced AKT phosphorylation, which is a component of the main cell survival pathway. We conclude that BAS-4 showed potential activity against glioma by inducing apoptosis mediated by ΔΨm loss and AKT pathway disruption, and future studies should further evaluate BAS-4 as a promising antineoplastic agent against glioblastoma.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER.

BACKGROUND: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. OBJECTIVE: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. METHODS: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. RESULTS: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. CONCLUSION: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

Antiproliferative and antiangiogenic effect of Amblyomma sculptum (Acari: Ixodidae) crude saliva in endothelial cells in vitro

Neovascularization, a process that includes vasculogenesis and angiogenesis, may be a physiological or pathologic event, but in any cases the phenomenon is related to the formation of vascular net and sprouting of endothelial cells from preexisting blood vessel. The tumor environment, which counts on the tumor cell proliferation, is plenty of proangiogenic factors, such as angiogenin, TGF (a and ß), FGF, VEGF, all of them playing a crucial role in angiogenesis, an important hallmark of cancer frequently related to a poor prognosis. Therefore, therapies focusing the inhibition of cancer neovasculogenesis have become an interesting strategy for the development of antitumor therapies. In this work, we investigate the effect of tick saliva on the human endothelial cells, in order to understand its inhibitory effects on angiogenesis. To this end, the HUVEC cells were used as model of angiogenesis in vitro and the anti-proliferative, anti-migratory, cytotoxicity was evaluated. Our data depicts that saliva impairs cell development by causing structural changes while precludes cell proliferation and migration, that are crucial events related to angiogenesis. Aiming the identification of the bioactive components related to antiangiogenic activity, saliva was analyzed through the Mass Spectrometry and among all molecules identified, disintegrins and cathepsin L seems to be primarily responsible for the antiangiogenic effects of saliva.

Anti-proliferative effect of terpenes on human prostate cancer cells: Natural sources and their potential role as chemopreventive agents / Efecto anti-proliferativo de los terpenos en células de cáncer de próstata humana: Fuentes naturales y su rol potencial como agentes quimiopreventivos

ABSTRACT Prostate cancer is one of the neoplastic diseases with the highest morbidity and mortality in the world. The diversity of available treatments and side effects related to therapeutic treatments are severe and affect a patient's quality of life. Thus, to creating new therapeutic alternatives to reduce morbidity and creating safe and effective therapies is a constant challenge. Recently, the use of traditional medicine and chemoprevention has gained importance. Several clinical and epidemiological studies suggest that a high-terpenoid compound-based diet is associated with a reduced risk of prostate cancer. This review is focused on the anti-proliferative effects of different terpenoids isolated from natural sources on human prostate cancer cells, with the aim of setting the basis to use these compounds as phytotherapeutic, nutraceutical and functional ingredients.

RESUMEN El cáncer de próstata es una de las neoplasias que produce gran morbilidad y mortalidad en el mundo. Los tratamientos y los efectos secundarios de la terapia son severos y afectan la calidad de vida del paciente. Por esto, es necesario crear nuevas alternativas terapéuticas para reducir la morbilidad y generar terapias seguras y efectivas es un desafío permanente. En los últimos años, el uso de la medicina tradicional y agentes quimiopreventivos han adquirido importancia. Estudios clínicos y epidemiológicos sugieren que una dieta basada en altas dosis de terpenoides se asocia a una reducción en el riesgo de presentar cáncer de próstata. Esta revisión se centra en los efectos anti-proliferativos sobre las células de cáncer de próstata en humanos de diferentes terpenoides aislados de fuentes naturales, con el objetivo de establecer las bases para utilizar estos compuestos como ingredientes fitoterapéuticos, nutracéuticos y funcionales.

Antioxidant, antimutagenic and antiproliferative activities in selected seaweed species from Sinaloa, Mexico.

Context Seaweeds from the Mexican Pacific Ocean have not been evaluated as a source of chemoprotectants. Objective The objective of this study is to evaluate chemopreventive activities of the seaweeds Phaephyceae - Padina durvillaei (Dictyotaceae) - Rodhophyceae - Spyridia filamentosa (Spyridiaceae), Gracilaria vermiculophylla (Gracilariaceae) - and Chlorophyceae - Ulva expansa (Ulvaceae), Codium isabelae (Codiaceae), Rhizoclonium riparium (Cladophoraceae) and Caulerpa sertularioides (Caulerpaceae). Materials and methods Methanol, acetone and hexane seaweed extracts were assessed at 30 and 3 mg/mL on antioxidant capacity (DPPH and ABTS assays), 0.003-3.0 mg/plate on antimutagenic activity against AFB1 using Salmonella typhimurium TA98 and TA100 tester strains in Ames test, and 12.5 to 100 µg/mL on antiproliferative activity on Murine B-cell lymphoma. Phenols, flavonoids and pigments content were also assessed as antioxidant compounds. Results Extraction yield was higher in methanol than in acetone and hexane extracts (6.4, 2.7 and 1.4% dw). Antioxidant capacity was higher in brown and green than in red seaweed species, particularly in P. durvillaei extracted in acetone (EC50 value= 16.9 and 1.56 mg/mL for DPPH and ABTS). Flavonoids and chlorophylls were identified as mainly antioxidant components; particularly in hexane extracts, which were correlated with the antioxidant capacity. Highest mutagenesis inhibition (> 40%) occurred in R. riparium at the lowest concentration assayed (0.003 mg/plate), while highest antiproliferative inhibition (37 and 72% for 12.5 and 25 µg/mL) occurred in C. sertularioides. Discussion and conclusion Flavonoids and chlorophylls explained the chemopreventive activities assessed in S. filamentosa, R. riparium and C. sertularioides. These seaweeds have a high potential as a source of novel chemoprotectants.

Antimutagenicity and antiproliferative studies of lipidic extracts from white shrimp (Litopenaeus vannamei).

An organic extract from fresh shrimp (Litopenaeus vannamei) was studied for antimutagenic and antiproliferative properties using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. Shrimp extract was sequentially fractionated by thin layer chromatography (TLC) and each fraction was tested for antimutagenic and antiproliferative activities. Crude organic extracts obtained from shrimp reduced the number of revertants caused by aflatoxina B(1), showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. These results suggested that the lipid fraction of the tested species contained compounds with chemoprotective properties that reduce the mutagenicity of AFB(1) and proliferation of a cancer cell line.