Combination of Antiglycative Polyphenols in Triple Negative Breast Cancer An in vitro study

Abstract

Triple Negative Breast Cancer TNBC is one of the most aggressive cancers in women Advanced Glycation End products AGEs are implied in genesis and metastasis of cancers via their receptor RAGE Considering the efficacy of preexistent plant derived anti cancer drugs the polyphenols Diosmin and Plumbagin were tested for their anti glycation potential and hence pertinence in curbing TNBC in vitro The polyphenolic anti glycation effect was confirmed using in vitro BSA glycation model Their combined and individual cytotoxicity was established using cell metabolic activity mitochondrial membrane potential cell cycle arrest redox status caspase 3 activity apoptosis and synergism pharmaco dynamic interaction analysis in high RAGE expressing p53 mutant MDA MB231 TNBC cells Molecular execution of cytotoxicity was derived by mRNA expression of apoptotic proteins Bax by Bcl minus 2 and metabolic metastatic regulators RAGE by by MGB1 by S100A4 Metabolic suppression apoptotic induction and metastatic inhibition coupled with transcriptional suppression of Bcl 2 RAGE HMGB1 S100A4 and up regulation of Bax and caspase minus 3 were achieved using the novel synergistic combination of anti glycative polyphenols Diosmin and Plumbagin for the first time with potent cytotoxic execution in MDA MB 231 cells Augmentation of cancer specific cytotoxicity and attenuation of normal cell toxicity were attained The polyphenols yielded dual cell cycle targeting G1 and Sphase arrest and redox balance shift favouring initial cancer cell apoptosis while later reimbursing the anti oxidant status thereby curbing chemo resistance and oncogenic resurgence respectively Polyphenolic suppression of RAGE and its ligands effectively elicited intrinsic apoptotic pathway in p53 mutant cancer cells Triple receptor negative breast cancer can be successfully curtailed using potent anti glycative polyphenolic combination targeting AGEs receptor RAGE and its ligands newline