Silibinin modulates UVB-induced apoptosis via mitochondrial proteins, caspases activation, and mitogen-activated protein kinase signaling in human epidermoid carcinoma A431 cells

Biochem Biophys Res Commun. 2004 Jul 16;320(1):183-9. doi: 10.1016/j.bbrc.2004.05.153.


Several recent studies by us have shown the strong chemopreventive efficacy of silibinin against both ultraviolet B (UVB) radiation and chemical carcinogen-induced tumorigenesis in mouse skin models. The molecular mechanisms underlying silibinin protective efficacy, however, are not completely known. Here, we examined the effect of silibinin on UVB-caused apoptosis in human epidermoid carcinoma A431 cells. Irradiation of cells with different doses of UVB (5-100 mJ/cm2) and different time periods (0.5-24h) resulted in a dose- and time-dependent increase in apoptosis (P < 0.05-0.001). Silibinin (100-200 microM) pre-treatment, however, resulted in an increase in UVB-induced apoptosis (P < 0.05-0.001); interestingly, its post-treatment caused a decrease in UVB-induced apoptosis (P < 0.05-0.001). A similar pattern in the activation of caspases-9, -3, and -7 was observed with these silibinin treatments. Further, silibinin treatment prior to or immediately after UVB exposure altered Bcl-2, Bax, Bak, and cytochrome c levels in mitochondria and cytosol in favor of or against apoptosis, respectively. Silibinin treatment prior to UVB also increased the activation of mitogen/stress activated protein kinases Erk1/2, JNK, and p38 kinase as compared to its post-treatment. Together, for the first time, our results demonstrate the role of mitochondrial apoptotic machinery and MAPK signaling cascade in silibinin-caused increase as well as protection in UVB-induced apoptosis in A431 cells, and suggest that similar mechanisms might be involved in preventive efficacy of silibinin against UVB-induced skin tumorigenesis.

Publication types

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

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Carcinoma, Squamous Cell / metabolism*
  • Caspases / metabolism*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Cell Line, Tumor / radiation effects
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Enzyme Activation
  • Humans
  • Mitochondrial Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Radiation Tolerance / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Ultraviolet Rays


  • Mitochondrial Proteins
  • Mitogen-Activated Protein Kinases
  • Caspases