Dietary flavonoids can prevent one third of cancer-related deaths in the United States possessing their ability to reduce oxidative stress which has implications in cancer development. Apigenin (4’,5,7-trihydroxyflavone), a flavone commonly present in plants such as camomilla, rosemary, parsley, celery and wheat germ has shown to possess anticancer properties. Apigenin has been reported to accumulate in various body organs including prostate gland and perturbs cancer development and progression through modulation of various signaling pathways. The cellular distribution of apigenin and its interaction with nucleic acids remains an important challenge for its development as chemopreventive agent. For these studies, we used various human prostate cancer cells viz. DU145, LNCaP and PC-3 and transformed human prostate epithelial RWPE1 cells. Incubation of LNCaP cells with 20 μM apigenin for 6 h exhibited an accumulation of 1.4 nmoles/million cells which was higher than in PC3 and DU145 by factor of 1.79 and 2.41, respectively. Almost similar uptake of apigenin was observed in RWPE1 cells as in LNCaP cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5μmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.31%), followed by cytosol (23.90%), nuclear membranes (17.86%) and microsomes (12.91%), respectively. Preferential apigenin retention by the nuclear matrix suggests its interaction with the nucleic acids and prompted further studies to determine the interactions of apigenin with DNA by using UV-Vis spectroscopic methods. Studies conducted with 0.25 mM DNA solution with varying concentrations of apigenin from .006 mM to 0.4mM and absorption spectral changes were recorded at 230 nm-450nm range. Detailed spectroscopic analysis of apigenin with DNA exhibited a marked decrease in the absorption intensity at 335 nm proportional to apigenin concentration indicating the possible intercalation of apigenin with DNA. Reciprocal plot analysis showed linearity and the stability of DNA-apigenin adduct with the magnitude of K=3.62×104 M-1. Furthermore, in vitro studies assessing the antioxidant potential of apigenin demonstrated that 0.25 mM DNA solution lost its spectral peak absorbance upon exposure to 15 mM dose of H2O2. However, the presence of apigenin at 0.4 mM and higher concentration prevented H2O2-mediated damage to DNA as indicated by the restoration of the peak absorbance of DNA. Taken together, our studies demonstrate that apigenin is readily taken up by prostate epithelial and cancer cells, has nuclear presence and its intercalation with nucleic acid bases, might be in part, accountable for its chemopreventive and antioxidant activities.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4632. doi:10.1158/1538-7445.AM2011-4632

©2011 American Association for Cancer Research
2011