Role of Oxidative Stress in Centchroman mediated Apoptosis: An in vitro study

Abstract

Breast Cancer (BC) continues to draw attention globally for various reasons for which Tamoxifen (TAM) is the treatment of choice. However, with the associated pros & cons of this drug, our attempt to position the CDRI developed, contraceptive Centchroman (CC) as an antineoplastic, has met with enormous success. Our studies employ the in vitro system for analyzing different modes of cell death using ER/PR +ve & -ve MCF-7/MDA MB-231 Human Breast Cancer Cells (HBCCs) respectively. The ligands investigated in the foregoing are CC/TAM & Curcumin (CUR, a phytoestrogen) separately & together. Since CC causes apoptosis in HBCCs as demonstrated by our group, efforts were made to analyze the contribution of Oxidative Stress and Autophagy in regulating cell death. Additionally, the study investigates whether CUR could help lower the dose and improve the efficacy of CC. The IC50 of CC in MCF-7/ MDA MB-231 was determined to be ~10/20μM. Upon using 10-50μM CUR as an adjuvant, the extent of antineoplasticity escalated significantly. However, CUR at physiological doses of < 5μM, failed to elicit the desired effect of cell killing. Moreover, the role of Redox Homeostasis & Stress Activated Protein Kinases (SAPKs) in regulating Apoptosis was concomitantly determined, demonstrating that both genomic & non-genomic pathways critically regulate the cybernetics of cell death. The dissertation therefore provides with an overview of how a common dietary ingredient can be co-opted to address BC. What is desired is to provide ways and means to modify & improve the bioavailability of CUR through classical & modern Structural-Functional-Chemistry for its eventual employment as an adjunct to CC. This study despite answering numerous questions raises many more, worth investigating.