Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.canlet.2003.11.028
Title: Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells
Authors: Zhang, S.
Ong, C.-N. 
Shen, H.-M. 
Keywords: AO, acridine orange
Apoptosis
BSO, buthionine sulfoximine
Calcium
EB, ethidium bromide
Glutathione
GSH, reduced glutathione
GSSG, oxidized glutathione
NAC, N-acetylcysteine
Parthenolide
PN, parthenolide
Reactive oxygen species
Thiol
Issue Date: 28-May-2004
Citation: Zhang, S., Ong, C.-N., Shen, H.-M. (2004-05-28). Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Letters 208 (2) : 143-153. ScholarBank@NUS Repository. https://doi.org/10.1016/j.canlet.2003.11.028
Abstract: Parthenolide is one of the main components responsible for the anti-inflammatory property of Feverfew. Recently, parthenolide has shown to induce apoptosis in cancer cells. Here we further studied the mechanism of parthenolide-induced apoptosis by focusing on the role of intracellular thiols and calcium in a human colorectal cancer cell, COLO 205. Parthenolide rapidly depleted intracellular thiols, including both free glutathione (GSH) and protein thiols. Concomitantly, there were dose- and time-dependent increases in intracellular reactive oxygen species (ROS) and calcium levels. Increased expression of GRP78 protein, a marker for endoplasmic reticulum stress was also detected. All these changes preceded parthenolide-induced apoptotic cell death. More importantly, pretreatment with N-acetylcysteine, a precursor of GSH synthesis, protected the cells from parthenolide-induced thiol depletion, ROS production, cytosolic calcium increase and completely blocked parthenolide-induced apoptosis. On the contrary, pretreatment of buthionine sulfoximine, an inhibitor of GSH synthesis sensitized the cell to apoptosis. These data clearly demonstrate that the intracellular thiols and calcium equilibrium play a critical role in parthenolide-induced apoptotic cell death. © 2003 Elsevier Ltd. All rights reserved.
Source Title: Cancer Letters
URI: http://scholarbank.nus.edu.sg/handle/10635/113423
ISSN: 03043835
DOI: 10.1016/j.canlet.2003.11.028
Appears in Collections:Staff Publications

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