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Pseudolaric Acid B Induces Apoptosis Through p53 and Bax/Bcl-2 Pathways in Human Melanoma A375-S2 Cells  

Gong Xian-Feng (China-Japan Research Institute of Medical and Pharmaceutical Sciences, Department of Pharmacology, Shen-yang Pharmaceutical University)
Wang Min-Wei (Department of Pharmacology, Shenyang Pharmaceutical university)
Tashiro Shin-Ichi (Department of Clinical and Biomedical Sciences, Showa Pharmaceutical university)
Onodera Satoshi (Department of Clinical and Biomedical Sciences, Showa Pharmaceutical university)
Ikejima Takashi (China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shen-yang Pharmaceutical University)
Publication Information
Archives of Pharmacal Research / v.28, no.1, 2005 , pp. 68-72 More about this Journal
Abstract
Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry, cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD). P53 protein expression was upregulated while cells were arrested at the $G_2/M$ phase of the cell cycle. There was a decrease in the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins, whereas pro-apoptotic Bax was increased. The two classical caspase substrates, PARP and ICAD, were both decreased in a time-dependent manner, indicating the activation of downstream caspases.
Keywords
Pseudolaric acid B; Apoptosis; A375-S2;
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