African Journal of
Pharmacy and Pharmacology

  • Abbreviation: Afr. J. Pharm. Pharmacol.
  • Language: English
  • ISSN: 1996-0816
  • DOI: 10.5897/AJPP
  • Start Year: 2007
  • Published Articles: 2250

Full Length Research Paper

Antitumor effects of cucurmosin in human chronic myeloid leukemia occur through cell cycle arrest and decrease the Bcl-2/Bax ratio to induce apoptosis

Jieming Xie1#*, Wenzhong Que2#, Minghuang Chen3, Jiancheng Sun1, Tinbo Liu4, Huili Liu4, Mei Liu4, Aiqin Yang1, Pei Yang4 and Yulu Wang1
1College of Pharmacy, Fujian Medical University, Fuzhou, 350005, China. 2The First Clinical Medical College of Fujian Medical University, Fuzhou, 350005, China. 3The State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, the Chinese Academy of Sciences, Fuzhou, 350002, China. 4Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou, 350005, China.
Email: [email protected]

  •  Accepted: 01 June 2011
  •  Published: 31 July 2011

Abstract

Cucurmosin, a novel type 1 ribosome-inactivating protein, induced cell death in various cell types including several tumor cell lines. However, the mechanism remained largely uncharacterized. In this study, we investigated the possible mechanism underlying its cytotoxicity by using K562 cells. In the study, typical characteristics of apoptosis, such as cell shrinkage, apoptotic bodies, cell cycle arrest and DNA fragmentation, were observed in cucurmosin treatment. The loss of the MMP (â–³ψm) and the content of cytochrome c in cytolis were increased in cucurmosin treatment. Cucurmosin-treated activated caspase-3, down regulated the expression of anti-apoptotic Bcl-2 protein and upregulated the expression of pro-apoptotic Bax protein, eventually leading to a decrease of the Bcl-2/Bax ratio in K562 cells. Down-regulation of p210Bcr-Abl protein level in cucurmosin treatment was observed. In addition, Hsp90, the molecular chaperone of p210bcr/abl was also down-regulated in cucurmosin treatment. Our data indicated that cucurmosin induced apoptosis of K562 cells by mitochondria dysfunction and the down-regulation of P210bcr/abl by disrupting molecular chaperone functions of Hsp90 might be also one of the mechanisms implicated in the cucurmosin-mediated apoptosis in the K562 cells. Thus, this study provided the rationale to investigate cucurmosin as a potential therapeutic agent for leukemia cells.

 

Key words: Cucurmosin, chronic myeloid leukemia, k562 cells, apoptosis.