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Biomol Ther (Seoul). 2016 Mar 1;24(2):147-55. doi: 10.4062/biomolther.2015.093.

Assessment of the Cytotoxic and Apoptotic Eἀects of Chaetominine in a Human Leukemia Cell Line.

Yao J1,2, Jiao R3, Liu C1,2, Zhang Y1,2, Yu W1,2, Lu Y1,2, Tan R3.

Author information

1
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
2
Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, PR China.
3
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.

Abstract

Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

KEYWORDS:

Apoptosis; Cytotoxic; K562 cell; Mitochondrial pathway

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