Effect of methyl Vanillate and methyl divanilate on breast cancer cells: regulation of the NADPH oxidase complex

Abstract

Cancer has its development through certain biological capabilities acquired by cells that include support for proliferative signaling, resistance to cell death, induction of angiogenesis, invasiveness and metastasis. Tumor cells are commonly exposed to stress conditions, environmental factors and deregulation in oxidative metabolism. Reactive Oxygen Species (ROS) behave as important regulators of cell signaling and can participate in several stages of tumor progression, such as proliferation, resistance to apoptosis, induction of angiogenesis, invasion and metastasis. Downregulation of oxidative metabolism is highly involved, as is the expression of NADPH oxidases (NOXes) and the production of Reactive Oxygen Species, playing a key role in the behavior of cancer cells. Breast cancer is the most common type of cancer among women around the world. Current treatment strategies are based on surgical removal of the tumor or radiation therapy followed by doxorubicin (DOX) chemotherapy, which has remarkable antitumor activity, but with several side effects. The search for new therapeutic regimens that potentiate the effects of DOX or allow dose reduction and protection of healthy tissues are essential. Plant derived compounds play a crucial role in modern medicine as an accessible and promising approach to cancer prevention and management. Flavonoids such as vanillin and vanillic acid, for example, have a protective effect against free radicals and lipid peroxidation, in addition to antitumor properties. New studies have shown that esters of vanillic acid, especially methyl vanillate, have potential antioxidant properties, presenting high lipophilicity and probable intracellular auto dimerization, as well as other vanilla. Given the reports and since there are no papers published so far, this study aims to evaluate the regulatory effect of methyl vanillate and methyl divanillate on NOXes in breast cancer cells. To this end, human breast cancer cells (MCF-7) and normal human breast cells (EB4a) will be cultured and maintained in conditions suitable for in vitro study. The effect of methyl vanillate and methyl divanillate on cytotoxicity, apoptosis, reactive oxygen species production, migratory capacity and proliferation will be evaluated; besides the analysis of genes of the NOXes by means of the Real-Time technique qPCR and Western Blot. (AU)