title: 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.affiliation: National Institute of Toxiological Research, Korea Food and Drug Administration, 5, Nokbun-dong, Eunpyung-gu, Seoul, South Korea.
authors.forename: Kwang Soo
authors.initials: KS
authors.lastname: Ahn
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Jung
authors.forename: Hai Kwan
authors.initials: HK
authors.lastname: Jung
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Chung
authors.forename: Ki Hwa
authors.initials: KH
authors.lastname: Yang
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hyeong Bae
authors.initials: HB
authors.lastname: Pyo
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Park
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Park
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D005434:Flow Cytometry; D006016:Glycolates / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007641:Keratolytic Agents / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000209:etiology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006016:Glycolates; D007641:Keratolytic Agents; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C031149:glycolic acid