Inhibitory effect of glycolic acid on ultraviolet B-induced c-fos expression, AP-1 activation and p53-p21 response in a human keratinocyte cell line.

Abstract

Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been commonly used as a cosmetic ingredient since it was known to have photo-protective and anti-inflammatory effects, and anti-oxidant effect in UV-irradiated skin. However, little has been known about the functional role of glycolic acid on UV-induced skin tumorigenesis. We previously found that glycolic acid inhibited UV-induced skin tumor development in hairless mouse. In this study we investigated anti-tumor promoting mechanism of glycolic acid on the UV-induced skin tumor development. The ability of glycolic acid to inhibit the UVB-induced cytotoxicity, apoptosis and expression of apoptosis-regulatory genes (p53 and p21) was examined. We also investigated whether glycolic acid could inhibit UVB-induced alternation of cell cycle, c-fos expression and activation of transcription factor AP-1 in cultured immortalized human keratinocyte HaCaT cells. Glycolic acid treatment attenuated the UVB-induced cell cytotoxicity as well as apoptosis. Glycolic acid also inhibited the UVB-induced expression of c-fos and the activation of transcription factor AP-1, and inhibited mRNA levels of apoptosis-regulatory gene (p53 and p21). These results suggest that glycolic acid may exert the inhibitory effect on the UVB-induced skin tumor development by blocking the UVB-induced of apoptosis and cytotoxicity through inhibition of c-fos expression and activation of AP-1 in addition to the inhibition of p53-p2l response pathway.

• Authors: Kwang Soo Ahn, Ki Sook Park, Kyung Mi Jung, Hai Kwan Jung, Sun Hee Lee, Soo Youn Chung, Ki Hwa Yang, Yeo Pyo Yun, Hyeong Bae Pyo, Yong Keun Park, Young Won Yun, Dae Joong Kim, Seung Min Park, Jin Tae Hong
• Journal: Cancer letters (Cancer Lett) Vol. 186 Issue 2 Pg. 125-35 (Dec 05 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 12213282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Glycolates
• Keratolytic Agents
• Proto-Oncogene Proteins c-fos
• RNA, Messenger
• Transcription Factor AP-1
• Tumor Suppressor Protein p53
• glycolic acid

Topics

• Apoptosis
• Blotting, Western
• Cell Nucleus (metabolism)
• Cell Survival
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (biosynthesis)
• Flow Cytometry
• Glycolates (metabolism, pharmacology)
• Humans
• Keratinocytes (metabolism)
• Keratolytic Agents (pharmacology)
• Proto-Oncogene Proteins c-fos (biosynthesis)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (etiology)
• Time Factors
• Transcription Factor AP-1 (metabolism)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (biosynthesis)
• Ultraviolet Rays