Pseudolaric acid B induces apoptosis in U937 human leukemia cells via caspase-9‑mediated activation of the mitochondrial death pathway.

Abstract

Numerous studies have demonstrated that pseudolaric acid B (PAB) promotes apoptosis in several cancer cell lines. However, thus far, the effect of PAB on human leukemia cells has not been evaluated. In the present study, the antitumor activity and molecular mechanisms of PAB in human leukemia U937 cells were investigated. It was demonstrated that PAB induced U937 cell apoptosis, which was confirmed by typical morphological changes and Annexin V‑fluorescein isothiocyanate staining. PAB was observed to activate a caspase‑dependent apoptotic pathway in U937 cells through the regulation of the Bcl‑2 family protein-mediated mitochondrial pathway. Furthermore, the activities of caspase‑3 and -9 were increased following treatment with PAB. In conclusion, to the best of our knowledge, this study demonstrated for the first time that PAB was able to enhance the apoptosis of U937 cells, at least in part, through the activation of the mitochondrial death pathway. Moreover, the activation of caspase‑3 and -9 mediated the apoptotic induction.

• Authors: Jia-He Wang, Liang Kan, Lin-Hua Shu, Nan Wang, Nai-Jing Li, Meng Zhang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 8 Issue 3 Pg. 787-93 (Sep 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 23827970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Diterpenes
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• pseudolaric acid B
• Caspase 3
• Caspase 9

Topics

• Antineoplastic Agents (chemistry, toxicity)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Diterpenes (chemistry, toxicity)
• Humans
• Leukemia (metabolism, pathology)
• Mitochondria (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• U937 Cells
• bcl-2-Associated X Protein (metabolism)