Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis.
Silymarin, derived from the milk thistle plant, Silybum marianum, has been traditionally used in the treatment of liver disease. Our previous study demonstrated that silymarin has an anti-apoptotic effect against UV irradiation. In this study, SIRT1, a human deacetylase that was reported to promote cell survival, was activated by silymarin (5 x 10(- 4) mol/L) in UV-irradiated human malignant melanoma, A375-S2 cells, followed by down-regulated expression of Bax and decreased release of cytochrome c. Cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly(ADP-ribose) polymerase (PARP), were also reduced. Consistent with its protective effect on UV-induced apoptosis, silymarin (5 x 10(- 4) mol/L) also increased G(2)/M phase arrest, possibly providing a prolonged time for efficient DNA repair. Consequently, that silymarin protected A375-S2 cell against UV-induced apoptosis was partially through SIRT1 pathway and modulation of the cell cycle distribution.
Li
L-H
LH
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
Wu
L-J
LJ
Tashiro
S-I
SI
Onodera
S
S
Uchiumi
F
F
Ikejima
T
T
D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D019610:Cytoprotection; D006801:Humans; D012838:Silymarin / Q000494:pharmacology*; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology*; D014466:Ultraviolet Rays
D012838:Silymarin; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins