The roles of Akt and MAPK family members in silymarin's protection against UV-induced A375-S2 cell apoptosis.

Abstract

Silymarin is a polyphenolic flavonoid derived from milk thistle (Silybum marianum) and has anti-inflammatory, cytoprotective as well as anticarcinogenic effects [Manna, S.K., Mukhopadlhyay, A., Van, N.T., Aggarwal, B., Silymarin suppresses TNF-induced activation of NF-kappaB, c-Jun N-terminal kinase, and apoptosis. J. Immunol. 1999; 163, 6800-6809.]. In this study, we assessed the effect of silymarin on ultraviolet light (UV)-induced cell apoptosis in human malignant melanoma, A375-S2 cells. Silymarin pre-treatment reversed the effect of UV irradiation on the expression of phosphorylated Akt and phosphorylated p53 (regulated by Akt activation), followed by down-regulation of Bax and up-regulated expressions of Bcl-2 and Bcl-xL proteins in UV-irradiated A375-S2 cells. Akt inhibitor decreased the viability of UV-irradiated cells which was treated with silymarin. In addition, the effect of UV irradiation on the phosphorylation of mitogen-activated protein kinase (MAPK) family members [extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)] was also reversed by silymarin. Moreover, ERK inhibitor (PD98059) and p38 inhibitor (SB203580) augmented UV-induced apoptosis in silymarin treated A375-S2 cells. Consequently, silymarin partially reduced UV-induced apoptosis by activating the Akt pathway, and silymarin's protective effect was also exerted by MAPK family members.

• Authors: Lin Hao Li, Li Jun Wu, Shin Ichi Tashiro, Satoshi Onodera, Fumiaki Uchiumi, Takashi Ikejima
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 6 Issue 2 Pg. 190-7 (Feb 2006) ISSN: 1567-5769 [Print] Netherlands
• PMID: 16399623 (Publication Type: Journal Article)

Chemical References

• Anthracenes
• Flavonoids
• Imidazoles
• Pyridines
• Silymarin
• bcl-2-Associated X Protein
• bcl-X Protein
• pyrazolanthrone
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• SB 203580
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Algorithms
• Anthracenes (pharmacology)
• Apoptosis (drug effects, radiation effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Down-Regulation
• Flavonoids (pharmacology)
• Genes, bcl-2 (genetics)
• Genes, p53 (genetics, physiology)
• Humans
• Imidazoles (pharmacology)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, physiology)
• Proto-Oncogene Proteins c-akt (physiology)
• Pyridines (pharmacology)
• Silymarin (pharmacology)
• Ultraviolet Rays
• bcl-2-Associated X Protein (genetics, physiology)
• bcl-X Protein (genetics)