Regulatory effect of resveratrol and prednisolone on MDR1 gene expression in acute lymphoblastic leukemia cell line (CCRF-CEM): An epigenetic perspective

Abstract

Chemotherapy is the most common method to treat leukemia as well as other types of human cancers. However, drug resistance has remained as the main challenge against the efficacy of treatments. Furthermore, having various adverse effects, chemotherapy drugs are becoming replaced by natural modalities for cancer therapy. In this regard, herbal components such as resveratrol and prednisolone have been identified to sensitize the leukemic cells to programmed cell death through a set of complex processes. In this study, we have examined DNA methylation on the human multidrug resistance gene 1 (MDR1) as a well-known marker for cellular drug resistance. We evaluated the effect of resveratrol and prednisolone on DNA methylation patterns of MDR1 gene promoter in the CCRF-CEM cell line as a representative for acute lymphoblastic leukemia. The study was aimed to clarify whether the MDR1 gene expression is regulated via DNA promoter methylation as a potential underlying mechanism, following exposure to resveratrol and prednisolone. Our data revealed that despite a strong influence to down-regulate the MDR1 expression, Resveratrol and Prednisolone did not alter the methylation pattern, suggesting other regulatory mechanisms in controlling the MDR1 expression in CCRF-CEM cell line. Unchanged status of DNA methylation of MDR1 gene may suggest that Resveratrol and Prednisolone causes the gene expression changes through a distinct mechanism which requires further studies to be understood. A more detailed understanding of the mechanisms beyond the regulation of the genes involved in cancer formation will help to design novel therapeutic strategies to fight the human cancers.