Changes in Glutathione, Oxidative Stress and Mitochondrial Membrane Potential in Apoptosis Involving the Anticancer Activity of Cantharidin Isolated from Redheaded Blister Beetles, Epicauta hirticornis

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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Changes in Glutathione, Oxidative Stress and Mitochondrial Membrane Potential in Apoptosis Involving the Anticancer Activity of Cantharidin Isolated from Redheaded Blister Beetles, Epicauta hirticornis



Anti-Cancer Agents in Medicinal Chemistry, 13(7): 1096-1114.

Author(s): Akalesh Kumar Verma and Surya Bali Prasad.

Affiliation: Zoology Department, North- Eastern Hill University, Shillong-793022, India.

Abstract

The present work describes the anticancer activity of cantharidin isolated from red-headed blister beetles, Epicauta hirticornis and its possible mode of action involving induction of apoptosis, oxidative stress and decrease in glutathione against murine ascites Dalton’s lymphoma. The structure of isolated compound was confirmed as cantharidin by X-ray diffraction method. Cantharidin treatment showed potent anticancer activity with an increase in life span (~ 87%) of tumor-bearing mice. Cantharidin treatment induced apoptosis in Dalton’s lymphoma cells and also caused an oxidative stress due to generation of reactive oxygen species (ROS) and an increase in lipid peroxidation. The observed canthardin-mediated decrease in glutathione and glutathione related enzymes activities in the tumor cells may weaken the cellular antioxidant system. Moreover, cantharidin treatment also caused a significant decrease in mitochondrial cytochrome c and simultaneous increase in cytosolic cytochrome c which ultimately facilitates activation of caspase 9 and 3 to augment mitochondrial apoptotic pathway causing cancer cell death. Based on the present findings, it may be suggested that cantharidin-mediated anticancer activity could be due to decrease in the protective ability of cancer cells by ROS and subsequent activation of effecter caspases leading to apoptotic cell death.

Keywords:

Antioxidant, Cytotoxicity, Docking, Glutathione reductase, Glutathione-S-transferase, Glutathione peroxidase.



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Article Details

Volume: 13
Issue Number: 7
First Page: 1096
Last Page: 1114
Page Count: 19
DOI: 10.2174/18715206113139990131
Price: $58
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