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Int. J. Mol. Sci. 2011, 12(6), 3831-3845; doi:10.3390/ijms12063831

Proliferation-Attenuating and Apoptosis-Inducing Effects of Tryptanthrin on Human Chronic Myeloid Leukemia K562 Cell Line in Vitro

Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, #17 West Changle Road, Xi’an 710032, China
Department of Pharmacy of Xijing Hospital, Xi’an 710032, China
Laboratory Animal Research Center, Xi’an 710032, China
Department of Obstetrics Gynecology, Xijing Hospital, Xi’an 710032, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 15 February 2011 / Revised: 30 May 2011 / Accepted: 31 May 2011 / Published: 10 June 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Tryptanthrin, a kind of indole quinazoline alkaloid, has been shown to exhibit anti-microbial, anti-inflammation and anti-tumor effects both in vivo and in vitro. However, its biological activity on human chronic myeloid leukemia cell line K562 is not fully understood. In the present study, we investigated the proliferation-attenuating and apoptosis-inducing effects of tryptanthrin on leukemia K562 cells in vitro and explored the underlying mechanisms. The results showed that tryptanthrin could significantly inhibit K562 cells proliferation in a time- and dose-dependent manner as evidenced by MTT assay and flow cytometry analysis. We also observed pyknosis, chromatin margination and the formation of apoptotic bodies in the presence of tryptanthrin under the electron microscope. Nuclei fragmentation and condensation by Hoechst 33258 staining were detected as well. The amount of apoptotic cells significantly increased whereas the mitochondrial membrane potential decreased dramatically after tryptanthrin exposure. K562 cells in the tryptanthrin treated group exhibited an increase in cytosol cyt-c, Bax and activated caspase-3 expression while a decrease in Bcl-2, mito cyt-c and pro-caspase-3 contents. However, the changes of pro-caspase-3 and activated caspase-3 could be abolished by a pan-caspase inhibitor ZVAD-FMK. These results suggest that tryptanthrin has proliferation-attenuating and apoptosis-inducing effects on K562 cells. The underlying mechanism is probably attributed to the reduction in mitochondria membrane potential, the release of mito cyt-c and pro-caspase-3 activation.
Keywords: tryptanthrin; chronic myeloid leukemia; proliferation; apoptosis; K562 cells tryptanthrin; chronic myeloid leukemia; proliferation; apoptosis; K562 cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Miao, S.; Shi, X.; Zhang, H.; Wang, S.; Sun, J.; Hua, W.; Miao, Q.; Zhao, Y.; Zhang, C. Proliferation-Attenuating and Apoptosis-Inducing Effects of Tryptanthrin on Human Chronic Myeloid Leukemia K562 Cell Line in Vitro. Int. J. Mol. Sci. 2011, 12, 3831-3845.

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