Trichostatin A and Zebularine along with E-cadherin re-expression enhance tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell cycle arrest in human breast adenocarcinoma cells

Abstract

Breast cancer is the leading cause of death among women in which its definite cure remains uncovered. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective killing towards cancer cells while sparing the healthy cells. However, it is limited by the development of TRAIL resistance. With the attempt to overcome TRAIL resistance, this research embarked to study the effect of epigenetic drugs, Trichostatin A (TSA) and Zebularine (Zeb) along with E-cadherin re-expression on anti-cancer effect in human breast adenocarcinoma cells. The MDA-MB-231 re-expressed with E-cadherin (231-EGFP) was treated with TSA and Zeb before being treated with TRAIL (TZT) to compare the effect on MDA-MB-231 and MCF-7. The cell viability, cell cycle and migration assays were conducted on these cells, prior to reverse-transcription-polymerase chain reaction (RT-PCR) targeted on proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 2 (CDK2), matrix metalloproteinase 9 (MMP9). TZT induced a significant increase in G0/G1-arrested cell population and reduction in cell viability in 231-EGFP. These were verified by the suppression of PCNA and CDK2 mRNA expression. However, there was a negligible effect to reduce the cell migration of the invasive MDA-MB-231 and 231-EGFP cells in accordance with the lack of down-regulation of MMP9. In conclusion, this research shows that TSA and Zeb have sensitized breast cancer towards TRAIL treatment in 231-EGFP cells, validating the potentiality of E-cadherin as a biomarker of TRAIL treatment efficacy in the invasive breast cancer.