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Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells

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An Erratum to this article was published on 22 May 2013

Abstract

Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.

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Abbreviations

GA:

Glycyrrhetinic acid

AEGA:

3-Acetyl-2-ene-glycyrrhetinic acid

DMSO:

Dimethyl sulphoxide

FBS:

Fetal bovine serum

MTT:

3-(4,5-dimethylthiazoyl)-2,5-diphenyltetrazolium bromide

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Acknowledgments

This work is supported in part by Zhejiang Provincial Natural Science Foundation of China (Y4110320), Natural Science Foundation of China (Nos. 20772071, 20972086) and the Opening Foundation of Biomedicine Engineering Key Discipline, Zhejiang, China (SWYX0901).

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The authors declare no conflict of interest.

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Correspondence to Chuanlian Xu.

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Gao, Z., Kang, X., Hu, J. et al. Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells. Cytotechnology 64, 421–428 (2012). https://doi.org/10.1007/s10616-011-9419-9

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  • DOI: https://doi.org/10.1007/s10616-011-9419-9

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