Synergistic effect of the association of methyl divanillate with chemotherapy in Triple Negative Breast Cancer cells

Abstract

Breast Cancer is the most common among women, with about 10 to 24% presenting in the triple negative (TNBC) invasive form, resulting in shorter survival and worse prognosis, including metastases to several organs. Enzymes such as metalloproteinases (MMP) are involved in metastasis, being responsible for the cleavage of extracellular matrix components allowing collagen degradation, as in the case of MMP-2 and -9. Transgelins, in turn, are the most recently studied actin-binding proteins, located in the cytoskeleton, and related to carcinogenesis, mainly transgelin-2 (T-2), which always exhibits increased levels in development and progression, especially in metastases, in addition to being related to chemotherapy resistance. Current chemotherapy consists of anthracyclines, taxanes, ixabepilone, platinum agents, as the only routine systemic treatment for patients with breast Cancer in general. However, this has many disadvantages for TNBC, mainly in the development of resistance to multiple drugs and the formation of secondary tumors. In this respect, the use of phytochemicals such as vanillin and vanillic acid and their esters play a crucial role in modern medicine as an accessible and promising approach. In view of the reports in the literature and previous work carried out by our research group as vanilloids and their dimers, and even though there are no works published so far, this study aims to evaluate the synergistic effect of methyl divanillate (DMV), dimer of Methyl Vanillate (MV), with chemotherapy drugs of first choice in Triple Negative Breast Cancer cells (MDA-MB-231) in 3D bioprinting. The synergistic effect of DMV with chemotherapy drugs of first choice, doxorubicin (DOX) and paclitaxel (PTX) on cytotoxicity, invasion, production of reactive oxygen species will be evaluated; in addition to gene expression and detection of MMP-2, -9, TIMP-1, -2 and T-2 by Real-Time qPCR and Western Blotting, respectively; In addition, the identification of total proteins present in cells exposed to the association of compounds and chemotherapy will be carried out, in order to identify possible biomarkers. (AU)