Abstract
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.
Highlights
Prostate cancer has the highest incidence of any cancer in American men and is the second leading cause of cancer-related mortality [1]
Our results demonstrate that apigenin preferentially accumulates in the nuclear matrix, binds to nucleic acid bases and has the ability to reduce oxidative DNA damage in prostate epithelial cells
In this study we explored cellular uptake of apigenin in transformed human prostate epithelial cells and various prostate cancer cells
Summary
Prostate cancer has the highest incidence of any cancer in American men and is the second leading cause of cancer-related mortality [1]. We have previously demonstrated that persistent chronic inflammation in the prostate gland, associated with increased accumulation of 8-OHdG in prostatic epithelium, promotes premalignant and malignant changes [9,11]. Reduced 8-OHdG levels, consistent with reduced oxidative stress, have been reported in subjects receiving plantbased diets rich in flavonoids and polyphenols [12,13,14,15]. These diets are characterized by conspicuous consumption of green tea and plant flavones rich in apigenin
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