Effects of Sulfur Containing Glycine Imine Derivatives Compounds on Multidrug Resistance Proteins (MRPs) and Apoptosis Mechanism in MCF-7 and DLD-1 Cell Lines

Abstract

Objective: Glutathione (GSH) is a tripeptide consisting of glycine, glutamic acid and cysteine. If the sulfur containing amino acids like methionine and cysteine increase in the cells, the level of GSH increases. GSH is one of the most important and powerful antioxidants in the body and it reduces oxidative stress. Reduction of GSH affects apoptosis activity and multidrug resistance proteins (MRPs). In the present study, we investigated the effects of sulfur- containing glycine imine derivatives on MRPs and apoptosis mechanism in the MCF-7 (breast cancer) and DLD-1 (colon cancer) cell lines. Methods: In MCF-7 and DLD-1 cell lines; mRNA levels of MRPs (ABCB1, ABCC3, ABCC10, ABCC11 and ABCG2), apoptosis mechanism proteins (BAX, BACL-2, P53, PARP, CASP3), heat shock proteins (HSPs) and endoplasmic reticulum chaperone proteins (GRPs) were determined by qRT-PCR method. Results: Compounds decreased gene expression of multiple drug resistance (MDR) genes and increased gene expression of pro- apoptosis mechanism genes (BAX, P53, CASP3). HSPs and BCL- 2 and PARP gene expressions decreased. There was no significant decrease in gene expression of GRPs. The compounds were shown to have remarkable effects on MDR genes (ABCB1, ABCC10, ABCC11 and ABCG2) other than ABCC3. Compounds were found to have significant effects on apoptosis mechanism genes and HSPs. Conclusion: Our results indicate that the sulfur-containing glycine imine derivatives can be a potent option as a cancer drug, especially in breast and colon cancers.