The roles of Akt and MAPK family members in silymarin's protection against UV-induced A375-S2 cell apoptosis.
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.
Li
Lin Hao
LH
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province, 110016, China.
Wu
Li Jun
LJ
Tashiro
Shin Ichi
SI
Onodera
Satoshi
S
Uchiumi
Fumiaki
F
Ikejima
Takashi
T
D000465:Algorithms; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012838:Silymarin / Q000494:pharmacology*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000502:physiology; D051020:bcl-X Protein / Q000235:genetics
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D012838:Silymarin; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C432165:pyrazolanthrone; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one