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

Biochem Biophys Res Commun. 2001 Oct 5;287(4):914-20. doi: 10.1006/bbrc.2001.5672.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Apigenin
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle / drug effects*
  • Cell Line
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cell Transformation, Viral
  • DNA / metabolism
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Male
  • Microscopy, Fluorescence
  • Prostate / cytology*
  • Prostate / drug effects
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Flavonoids
  • Apigenin
  • DNA