Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells.

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 G2/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.

• Authors: Xian-Feng Gong, Min-Wei Wang, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 28 Issue 1 Pg. 68-72 (Jan 2005) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 15742811 (Publication Type: Comparative Study, Journal Article)

Chemical References

• BAX protein, human
• Diterpenes
• Growth Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• pseudolaric acid B

Topics

• Apoptosis (drug effects, physiology)
• Cell Line, Tumor
• Diterpenes (pharmacology)
• Dose-Response Relationship, Drug
• Growth Inhibitors (pharmacology)
• Humans
• Melanoma (genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics, physiology)
• Signal Transduction (drug effects, physiology)
• Tumor Suppressor Protein p53 (biosynthesis, genetics)
• bcl-2-Associated X Protein