Induction of apoptosis by sulforaphane and curcumin and expression profile of jmjd3, a key histone demethylase in breast cancer cell line MDA-MB-231

Abstract

Breast cancer is one of the most common forms of cancer occurring in females resulting in to high rate of mortality worldwide. Uncontrolled cell proliferation leads to cancer which may be attributed to genetic mutations or epigenetic alterations in the genome. Deregulations of epigenetic mechanisms are highly associated with cancer progression. Uncontrolled cell proliferation and evasion of apoptosis are important hall marks of cancer progression. Hence in this study we have investigated the role of sulforaphane and curcumin in the induction of apoptosis in metastatic adenocarcinoma MDA MB-231 cells. As aberrant Histone methylation and demethylation pathways are most commonly associated with breast cancer progression we have also tried to investigate the expression profile of jmjd3, a key histone demethylase, at transcriptome level after treatment with of sulforaphane and curcumin for 24 hours. This investigation also aimed at finding a correlation between jmjd3 expression and induction of apoptosis in breast cancer cell line MDA MB-231. The down regulation of anti apoptotic gene Bcl-2 and up regulation of pro apoptotic gene Bax along with formation of chromatin condensation, DNA fragmentation and DNA damage suggests that there is induction of apoptosis in response to the sulphoraphane and curcumin treatment for 24 hours at their corresponding IC50 values. From all this investigations we can presume that may be these natural polyphenols are mediating their effect on cancer cells at transcriptome level by inducing apoptosis related genes. Moreover the down regulation of jmjd3 and down regulation of Bcl-2 with treatment of sulphoraphane and curcumin may be correlated to have a conjoint effect on apoptosis induction in breast cancer cells. Further studies at protein level may unravel hidden dimensions of jmjd3 in the induction of apoptosis in breast cancer cells which may create a better therapeutic avenue for treating cancer patients in future.