Silibinin inhibits ultraviolet B radiation-induced mitogenic and survival signaling, and associated biological responses in SKH-1 mouse skin

Carcinogenesis. 2005 Aug;26(8):1404-13. doi: 10.1093/carcin/bgi096. Epub 2005 Apr 14.


Ultraviolet B (UVB) radiation is a complete skin carcinogen causing DNA damage as a tumor-initiating event and activating signaling cascades that play a critical role in its tumor-promoting potential. Recently we reported that a naturally occurring flavonoid, silibinin, protects UVB-induced skin damages and prevents photocarcinogenesis. Here we examined silibinin efficacy on acute and chronic UVB-caused mitogen-activated protein kinases (MAPKs) and AKT activation and associated biological responses in SKH-1 hairless mouse skin. A single UVB exposure at 180 mJ/cm2 dose resulted in varying degrees of ERK1/2, JNK1/2, MAPK/p38 and AKT phosphorylation at various time-points in mouse skin; however, topical application of silibinin prior to or immediately after UVB exposure, or its dietary feeding strongly inhibited the activation of these molecules at all the time-points examined. Stronger effects of silibinin towards inhibition of UVB-caused phosphorylation of MAPKs and AKT were also observed in a chronic UVB (180 mJ/cm2/day for 5 days) exposure protocol. Immunohistochemical analysis of chronically exposed skin sections showed that silibinin treatment in all three protocols increases UVB-induced p53-positive cells and decreases UVB-caused cell proliferation, apoptotic and sunburn cells. These findings suggest that silibinin inhibits UVB-induced MAPK and AKT signaling and increases p53 in mouse skin, and that these effects of silibinin possibly lead to a decrease in UVB-caused proliferation and apoptosis, which might, in part, be responsible for its overall efficacy against photocarcinogenesis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Female
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Hairless
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / radiation effects
  • Proliferating Cell Nuclear Antigen / analysis
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / radiation effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / radiation effects
  • Proto-Oncogene Proteins c-akt
  • Radiation-Protective Agents / pharmacology*
  • Silybin
  • Silymarin / pharmacology
  • Skin / radiation effects*
  • Tumor Suppressor Protein p53 / analysis
  • Ultraviolet Rays*


  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins
  • Radiation-Protective Agents
  • Silymarin
  • Tumor Suppressor Protein p53
  • Silybin
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases