Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin

Jen K. Lin, Yen Chou Chen, Ying Tang Huang, Shoei Y. Lin-Shiau

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Apigenin, a less-toxic and non-mutagenic flavonoid, suppressed 12-0- tetradecanoyl-phorbol-13-acetate-(TPA)-mediated tumor promotion of mouse skin. TPA had the ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene expression. Our study indicates that apigenin inhibited PKC by competing with adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression. Curcumin, a dietary pigment phytopolyphenol, is also a potent inhibitor of tumor promotion induced by TPA in mouse skin. When mouse fibroblast cells were treated with TPA alone, PKC translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 μM curcumin for 15 min inhibited TPA-induced PKC activity in the particulate fraction by 26-60%. Curcumin also inhibited PKC activity in vitro by completing with phosphatidylserine. Curcumin (10 μM) suppressed the expression of c-jun in TPA-treated cells. Fifteen flavonoids were examined for their effects on morphological changes in soft agar and cellular growth in v-H-ras transformed NIH3T3 cells. The results demonstrated that only apigenin, kaempferol, and genistein exhibited the reverting effect on the transformed morphology of these cells. Based on these findings, it is suggested that the suppression of PKC activity and nuclear oncogene expression might contribute to the molecular mechanisms of inhibition of TPA- induced tumor promotion by apigenin and curcumin.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalJournal of Cellular Biochemistry
Volume67
Issue numberSUPPL. 28/29
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Apigenin
  • C-fos
  • C-jun
  • Curcumin
  • Genistein
  • Kaempferol
  • PKC
  • PTK

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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