Introduction: Epidemiological studies indicate that diet rich in fruits and vegetables is associated
with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents.
The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols
have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases
(DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs
were planned to examine genistein’s role as a natural epigenetic modifier in human cervical cancer cells, HeLa.
Methods: Expression of the tumour suppressor genes (TSGs) [MGMT, RARβ, p21, E-cadherin, DAPK1] as
well the methylation status of their promoters were examined alongwith the activity levels of DNMT and HDAC
enzymes after treatment with genistein. Expression of DNMTs and HDACs was also studied. In-silico studies
were performed to determine the interaction of genistein with DNMTs and HDACs.
Results: Genistein treatment significantly reduced the expression and enzymatic activity of both DNMTs and
HDACs in a time-dependent way. Molecular modeling data suggest that genistein can interact with various
members of DNMT and HDAC families and support genistein mediated inhibition of their activity. Timedependent
exposure of genistein reversed the promoter region methylation of the TSGs and re-established their
Conclusions: In this study, we find that genistein is able to reinstate the expression of the TSGs studied by
inhibiting the action of DNMTs and HDACs. This shows that genistein could be an important arsenal in the
development of epigenetic based cancer therapy.