Glaucocalyxin A and B-induced Cell Death is Related to GSH Perturbation in Human Leukemia HL-60 Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
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Glaucocalyxin A and B-induced Cell Death is Related to GSH Perturbation in Human Leukemia HL-60 Cells



Anti-Cancer Agents in Medicinal Chemistry, 13(8): 1280-1290.

Author(s): Wen Hua Yang, Zhen Zhang, Yang Hu Sima, Jian Zhang and Jian Wen Wang.

Affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Abstract

Glaucocalyxin (Gla) A-C are major ent-kauranoid diterpenoids isolated from Rabdosia japonica var. glaucocalyx, a plant used in Chinese traditional medicine as an antitumor and anti-inflammatory agent. The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in Gla -induced cytotoxicity. Among major ent-kauranoid diterpenoids isolated, Gla A and B dose-dependently decreased the growth of HL-60 cells with an IC50 of approximately 6.15 and 5.86 µ M at 24 h, respectively. Both Gla A and B could induce apoptosis, G2/M-phase cycle arrest, DNA damage and the accumulation of reactive oxygen species (ROS) in HL-60 cells. Moreover, Gla A, B caused rapid decrease of the intracellular GSH content, while inhibition of cellular GSH synthesis by buthionine sulfoximine (BSO) augmented the induced cytotoxicity and apoptosis in HL-60 cells. On the other hand, the administration of GSH or GSH precursor N-acetyl-cysteine (NAC) could rescue Gla A, B-depleted cellular GSH, and abrogate the induced cytotoxicity, G2/M-phase cycle arrest, DNA damage and ROS accumulation in HL-60 cells. Furthermore, Gla A, B decreased the activity of the GSH-related enzymes including glutathione reductase (GR) and glutathione peroxidase (GPX). These data suggest that the intracellular GSH redox system plays important roles in regulating the Gla A, B-induced cytotoxicity on HL-60 cells.

Keywords:

Apoptosis, Glaucocalyxin A, B and C, Glutathione, HL-60 cells, Reactive oxygen species.



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Article Details

Volume: 13
Issue Number: 8
First Page: 1280
Last Page: 1290
Page Count: 11
DOI: 10.2174/18715206113139990200
Price: $58
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