Changes in glutathione, oxidative stress and mitochondrial membrane potential in apoptosis involving the anticancer activity of cantharidin isolated from redheaded blister beetles, epicauta hirticornis.
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.
Cell and Tumor Biology Laboratory, North Eastern Hill University, Shillong-793022, India.
Akalesh Kumar
AK
Verma
Surya Bali
SB
Prasad
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002193:Cantharidin / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D001517:Coleoptera / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D002193:Cantharidin