MCF-7 and MDA-MB-231, human breast cancer cell lines were used for <i>in vitro</i> studies to evaluate toxic effects of armed virus, rMV-BNiP3 both as a standalone therapy and in combination with paclitaxel or H2 compound, a hydrazone derivative.
Here we confirm that bafilomycin A1 (BafA1), a selective vATPase inhibitor, significantly increased death of breast cancer cells in a hypoxia and Bnip3-dependent manner and significantly reduced tumor growth in MCF7 and MDA-MB-231 mouse xenografts.
Our recent study showing association of hyperhomocysteinemia and hypomethioninemia in breast cancer and other studies indicating association of hyperhomocysteinemia with metastasis and development of drug resistance in breast cancer cells treated with homocysteine lead us to hypothesize that homocysteine might modulate the expression of certain tumor suppressors, i.e., RASSF1, RARβ1, CNND1, BRCA1, and p21, and might influence prognostic markers such as BNIP3 by inducing epigenetic alteration.
Consistent with these results, a significant inverse correlation was observed in the expression of FAS and BNIP3 in clinical samples of human breast cancer.