title: Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells.
abstract: Agents that are capable of inducing selective apoptosis of cancer cells are receiving considerable attention in developing novel cancer-preventive approaches. In the present study, employing normal human prostate epithelial cells (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 in fruits and vegetables. Apigenin treatment to NHPE and PZ-HPV-7 resulted in almost similar growth inhibitory responses of low magnitude. In sharp contrast, apigenin treatment resulted in a significant decrease in cell viability of CA-HPV-10 cells. Similar selective growth inhibitory effects were also observed for human epidermoid carcinoma A431 cells compared to normal human epidermal keratinocytes. Apigenin treatment resulted in significant apoptosis of CA-HPV-10 cells as evident from (i) DNA ladder assay, (ii) fluorescence microscopy, and (iii) TUNEL assay, whereas the NHPE and PZ-HPV-7 cells did not undergo apoptosis but showed exclusive necrotic staining only at a high dose of 40 microM. Apigenin (1-10 microM) also resulted in a dose-dependent G2-M phase cell cycle arrest of CA-HPV-10 cells but not of PZ-HPV-7 cells. The growth-inhibitory and apoptotic potential of apigenin was also observed in a variety of prostate carcinoma cells representing different stage and androgen responsiveness. Apigenin may be developed as a promising chemopreventive and/or chemotherapeutic agent against prostate cancer.
authors.affiliation: Department of Dermatology, Case Western Reserve University, Research Institute of University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA. gxs44@po.cwru.edu
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: F
authors.initials: F
authors.lastname: Afaq
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D011467:Prostate / Q000166:cytology* / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D047310:Apigenin; D004247:DNA