Evaluating the effect of a polyphenolic compound on miR-21 expression in breast cancer

Abstract

Breast cancer is one of the major causes of deaths among women worldwide. Micro-RNAs have a crucial role in the formation and progression of breast cancer, and their profiles are altered throughout the disease's pathogenesis. The expression of oncogenic microRNAs is greatly elevated in cancer cells as well as resistant cells. Some polyphenolic compounds, such as quercetin, hesperidin, stevioside, and pterostilbene, have been demonstrated to inhibit the advancement of breast cancer, however their activities in altering microRNA expressions are unknown. It is also not clear whether they are effective against the resistant breast cancer model. As a result, the goal of this work is to see how effective polyphenolic compounds are at modulating the expressions of mir-21, involved in breast cancer aetiology in vitro. In this study, we aimed to establish chemoresistant using 5-Fluorouracil (5-FU) and hormonal resistant using tamoxifen- breast cancer cell models, in a dose dependent manner. Interaction of most effective phytochemicals and their interaction with miR-21 has been assessed by in silico docking. Further validation of this in silico result has been confirmed by in vitro MTT assay and the most effective phytochemical, stevioside, was used in cancer specific assays. Effect of stevioside in the cancer cell apoptosis, cell proliferation and cell migration were tested by acridine orange-ethidium bromide staining, wound healing assay and trans-well assay. Effectiveness of this phytochemical showed potential to act as an anti-cancer agent in both 5 FU and tamoxifen resistant cells. Therefore, the study aims to diminish the problem of resistance development in breast cancer against chemotherapy and hormone therapy with the help of natural products.