Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures

Adnan O. Abu-Yousif, Kimberly A. Smith, Spiro Getsios, Kathleen J. Green, Rukiyah T. Van Dross, Jill C. Pelling

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Topical application of the bioflavonoid 4′,5,7-trihydroxyflavone (apigenin) to mouse skin effectively reduces the incidence and size of skin tumors caused by UVB exposure. The ability to act as a chemopreventive compound indicates that apigenin treatment alters the molecular events initiated by UVB exposure; however, the effects of apigenin treatment on UVB-irradiated keratinocytes are not fully understood. In the present study, we have used three models of human keratinocytes to study the effect of apigenin treatment on UVB-induced apoptosis: HaCaT human keratinocyte cells, primary keratinocyte cultures isolated from human neonatal foreskin, and human organotypic keratinocyte cultures. Each keratinocyte model was exposed to a moderate dose of UVB (300-1,000 J/m2), then treated with apigenin (0-50 μmol/L), and harvested to assess apoptosis by Western blot analysis for poly(ADP)ribose polymerase cleavage, annexin-V staining by flow cytometry, and/or the presence of sunburn cells. Apigenin treatment enhanced UVB-induced apoptosis >2-fold in each of the models tested. When keratinocytes were exposed to UVB, apigenin treatment stimulated changes in Bax localization and increased the release of cytochrome c from the mitochondria compared with UVB exposure alone. Overexpression of the antiapoptotic protein Bcl-2 and expression of a dominant-negative form of Fas-associated death domain led to a reduction in the ability of apigenin to enhance UVB-induced apoptosis. These results suggest that enhancement of UVB-induced apoptosis by apigenin treatment involves both the intrinsic and extrinsic apoptotic pathways. The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin.

Original languageEnglish (US)
Pages (from-to)3057-3065
Number of pages9
JournalCancer Research
Volume68
Issue number8
DOIs
StatePublished - Apr 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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