title: 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.affiliation: Sun Yat-sen University, Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Tian-He Road 600, Guangzhou, Guangdong 510630, PR China. liujj@gzsums.edu.cn
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Ren-Wei
authors.initials: RW
authors.lastname: Huang
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Lin
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Xianglin
authors.initials: X
authors.lastname: Pan
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Song
authors.forename: Mao-Hong
authors.initials: MH
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006690:Bisbenzimidazole / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D053938:DNA Fragmentation; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism*; D008956:Models, Chemical; D010936:Plant Extracts / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C090365:ponicidin; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D006690:Bisbenzimidazole