Melanoma is the leading cause of
skin cancer-related deaths. We have examined the effect of
green tea polyphenols (GTPs), a natural mixture of
epicatechin monomers, on
melanoma cancer cell growth and the molecular mechanism underlying these effects using different human
melanoma cell lines as an in vitro model. Treatment of
melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of
melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of
histone deacetylase (HDAC) activity, reduction in the levels of class I
HDAC proteins, enhancement of
histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in
melanoma cells. GTPs-induced decrease in the levels of class I
HDAC proteins is mediated through proteasomal degradation.
Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of
melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of
cyclins and
cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of
tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).