Oxidative stress has been linked to prostate
carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage.
Apigenin, a dietary plant
flavone, possesses anti-proliferative and anticancer effects; however, its
antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of
apigenin, it's binding to
DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and
prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to
apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of
apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of
apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of
apigenin with
calf-thymus DNA exhibited intercalation as the dominant binding mode to
DNA duplex.
Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in
reactive oxygen species levels. In addition,
apigenin exposure suppressed the formation of 8-hydroxy-2'
deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that
apigenin is readily taken up by normal prostatic epithelial cells and
prostate cancer cells, and is incorporated into their nuclei, where its intercalation with
nucleic acid bases may account for its
antioxidant and chemopreventive activities.