Glaucocalyxin A and B-induced cell death is related to GSH perturbation in human leukemia HL-60 cells.

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 µM 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.

• Authors: Wen Hua Yang, Zhen Zhang, Yang Hu Sima, Jian Zhang, Jian Wen Wang
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 13 Issue 8 Pg. 1280-90 (Oct 2013) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 23796245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes, Kaurane
• Reactive Oxygen Species
• Buthionine Sulfoximine
• glaucocalyxin A
• glaucocalyxin B
• Glutathione Peroxidase
• Glutathione Reductase
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Apoptosis (drug effects)
• Buthionine Sulfoximine (pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Diterpenes, Kaurane (pharmacology)
• Glutathione (metabolism)
• Glutathione Peroxidase (metabolism)
• Glutathione Reductase (metabolism)
• HL-60 Cells
• Humans
• Reactive Oxygen Species (metabolism)