Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells

Agents that are capable of inducing selective apoptosis of cancer cells are receiving considerable attention in developing novel cancer-preventive app roaches. In the present study, employing normal human prostate epithelial c ells (NHPE), virally transformed normal human prostate epithelial cells (PZ -HPV-7), and human prostate adenocarcinoma (CA-HPV-10) cells, we evaluated the growth-inhibitory effects of apigenin, a flavonoid abundantly present i n fruits and vegetables. Apigenin treatment to NHPE and PZ-HPV-7 resulted i n almost similar growth inhibitory responses of low magnitude. In sharp con trast, apigenin treatment resulted in a significant decrease in cell viabil ity of CA-HPV-10 cells. Similar selective growth inhibitory effects were al so observed for human epidermoid carcinoma A431 cells compared to normal hu man epidermal keratinocytes. Apigenin treatment resulted in significant apo ptosis of CA-HPV-10 cells as evident from (i) DNA ladder assay, (ii) fluore scence microscopy, and (iii) TUNEL assay, whereas the NHPE and PZ-HPV-7 cel ls did not undergo apoptosis but showed exclusive necrotic staining only at a high dose of 40 muM. Apigenin (1-10 muM) also resulted in a dose-depende nt G2-M phase cell cycle arrest of CA-HPV-10 cells but not of PZ-HPV-7 cell s. The growth-inhibitory and apoptotic potential of apigenin was also obser ved in a variety of prostate carcinoma cells representing different stage a nd androgen responsiveness. Apigenin may be developed as a promising chemop reventive and/or chemotherapeutic agent against prostate cancer. (C) 2001 A cademic Press.