(-)-Epicatechin Inhibits Metastatic-Associated Proliferation, Migration, and Invasion of Murine Breast Cancer Cells In Vitro
Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant adverse effects. (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells.
CHARACTERIZATION OF THE CYTOTOXIC EFFECTSOF THE COMBINATION OF CISPLATIN AND FLAVANOL(-)-EPICATECHIN ON HUMAN LUNG CANCER CELL LINE A549. AN ISOBOLOGRAPHIC APPROACH
Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added si- multaneously with cisplatin. Materials and Methods: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed.
Anticancer potential of (−)-epicatechin in atriple-negative mammary gland model
Objectives The main aim of this work was to analyse the potential tumour growth inhibition effects
of (−)-epicatechin (EC). Triple-negative breast cancer (TNBC) is an invasive form of cancer charac-
terized by the absence of progesterone receptor, estrogen receptor and human epidermal growth
factor receptor 2. Doxorubicin (DOX) is widely used for its anti-tumour activity. EC belongs to the
flavanol subfamily and is a candidate molecule for the adjuvant treatment of cancer due to its
antiproliferative activities.
Methods Evaluation of EC effects and pathways involved in a model of TNBC.
Key findings EC inhibited tumour growth as efficiently as DOX (inhibition rates of 74% and 79% for
EC and DOX, respectively). The evaluation of adenosine monophosphate-activated protein kinase
(AMPK) and Akt phosphorylation and mTOR expression indicates that EC modulates these path-
ways, resulting in the inhibition of cell proliferation. Additionally, we found an increase in the sur-
vival of EC-treated animals compared with control-treated animals. This effect was similar to the
effects induced by DOX (survival rates of 44% and 30% for EC and DOX, respectively).
Conclusion EC has antiproliferative properties and increases survival in a model of TNBC. These ef-
fects may occur through the modulation of deregulated AMPK and Akt/mTOR signalling pathways.