Antiproliferation effects of ponicidin on human myeloid leukemia cells in vitro.

Abstract

Ponicidin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Ponicidin has been reported to have anti-tumor effects on a large variety of malignant diseases. In this study, we investigated the anti-proliferation effects of ponicidin on human myeloid K562 and HL-60 cells. Cell viability was measured by MTT assay; cell apoptosis was assessed by flow cytometry, DNA fragmentation analysis and Hoechst 33258 staining. Caspase-3 and poly(ADP-ribose) polymerase (PARP) activation and Bax and Bcl-2 expression were detected by Western blot analysis. The results revealed that ponicidin could significantly inhibit the growth of K562 and HL-60 cells by induction of apoptosis. The suppression was both time- and dose-dependent. Cell apoptosis was observed clearly after the cells were treated with ponicidin for 48-72 h. Western blotting showed cleavage of the caspase-3 zymogen protein (32 kDa) with the appearance of its 17 kDa subunit, together with a cleaved 89-kDa fragment of 116 kDa PARP when apoptosis occurred. Bcl-2 expression was down-regulated while Bax expression up-regulated concurrently when the cells were treated with ponicidin for 24-48 h. Therefore, we conclude that ponicidin has significant anti-proliferation effects by induction of apoptosis on myeloid leukemia cells in vitro, down-regulation of Bcl-2, and up-regulation of Bax, and that activation of caspase-3 and PARP may be an important apoptosis-inducing mechanism. The results suggest that ponicidin may serve as a potential therapeutic agent for leukemia.

• Authors: Jia-Jun Liu, Ren-Wei Huang, Dong-Jun Lin, Xiang-Yuan Wu, Qu Lin, Jun Peng, Xianglin Pan, Yu-Qin Song, Mao-Hong Zhang, Ming Hou, Feng Chen
• Journal: Oncology reports (Oncol Rep) Vol. 13 Issue 4 Pg. 653-7 (Apr 2005) ISSN: 1021-335X [Print] Greece
• PMID: 15756438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BAX protein, human
• Diterpenes
• Drugs, Chinese Herbal
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• ponicidin
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• Caspase 3
• Caspases
• Bisbenzimidazole

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Bisbenzimidazole (pharmacology)
• Blotting, Western
• Caspase 3
• Caspases (metabolism)
• Cell Proliferation
• Cell Survival
• DNA Fragmentation
• Diterpenes (pharmacology)
• Dose-Response Relationship, Drug
• Down-Regulation
• Drugs, Chinese Herbal
• Flow Cytometry
• HL-60 Cells
• Humans
• In Vitro Techniques
• K562 Cells
• Leukemia, Myeloid (drug therapy, metabolism)
• Models, Chemical
• Plant Extracts (pharmacology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Time Factors
• Up-Regulation
• bcl-2-Associated X Protein