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Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells.
Biochem Pharmacol. 2004 Nov 01; 68(9):1857-67.BP

Abstract

The effect of GSH depletion on mitochondrial damage and cell death due to mitomycin c (MMC) was assessed in small cell lung cancer (SCLC) cells. Cytotoxicity of MMC was attenuated by Tempol and dicumarol, inhibitors of the enzymatic reduction, and increased by xanthine oxidase. The MMC-induced cell death and decrease in the GSH contents in SCLC cells were inhibited by caspase inhibitors (z-DQMD.fmk, z-IETD.fmk and z-LEHD.fmk) and antioxidants (N-acetylcysteine, dithiothreitol and N-(2-mercaptopropionyl)glycine, melatonin, rutin and carboxy-PTIO). Thiol compounds, melatonin and rutin attenuated the MMC-induced nuclear damage, decrease in mitochondrial transmembrane potential, release of cytochrome c and activation of caspase-3. Treatment of MMC caused a significant decrease in GSH contents in SCLC cells, which was followed by increase in the formation of reactive oxygen species. Depletion of GSH due to L-buthionine sulfoximine enhanced the MMC-induced activation of caspase-3 and cell death in SCLC cells. Antioxidants, including N-acetylcysteine, depressed formations of nitric oxide, malondialdehyde and carbonyls due to MMC in SCLC cells. The results show that the reductive activation of MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to caspase-3 activation, and by activation of caspase-8. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by decrease in the intracellular GSH contents due to oxidative attack of free radicals.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15450951

Citation

Lee, Chung Soo, et al. "Effect of Change in Cellular GSH Levels On Mitochondrial Damage and Cell Viability Loss Due to Mitomycin C in Small Cell Lung Cancer Cells." Biochemical Pharmacology, vol. 68, no. 9, 2004, pp. 1857-67.
Lee CS, Park SY, Ko HH, et al. Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells. Biochem Pharmacol. 2004;68(9):1857-67.
Lee, C. S., Park, S. Y., Ko, H. H., & Han, E. S. (2004). Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells. Biochemical Pharmacology, 68(9), 1857-67.
Lee CS, et al. Effect of Change in Cellular GSH Levels On Mitochondrial Damage and Cell Viability Loss Due to Mitomycin C in Small Cell Lung Cancer Cells. Biochem Pharmacol. 2004 Nov 1;68(9):1857-67. PubMed PMID: 15450951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells. AU - Lee,Chung Soo, AU - Park,Se Young, AU - Ko,Hyun Hee, AU - Han,Eun Sook, PY - 2004/02/04/received PY - 2004/06/14/accepted PY - 2004/9/29/pubmed PY - 2004/12/16/medline PY - 2004/9/29/entrez SP - 1857 EP - 67 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 68 IS - 9 N2 - The effect of GSH depletion on mitochondrial damage and cell death due to mitomycin c (MMC) was assessed in small cell lung cancer (SCLC) cells. Cytotoxicity of MMC was attenuated by Tempol and dicumarol, inhibitors of the enzymatic reduction, and increased by xanthine oxidase. The MMC-induced cell death and decrease in the GSH contents in SCLC cells were inhibited by caspase inhibitors (z-DQMD.fmk, z-IETD.fmk and z-LEHD.fmk) and antioxidants (N-acetylcysteine, dithiothreitol and N-(2-mercaptopropionyl)glycine, melatonin, rutin and carboxy-PTIO). Thiol compounds, melatonin and rutin attenuated the MMC-induced nuclear damage, decrease in mitochondrial transmembrane potential, release of cytochrome c and activation of caspase-3. Treatment of MMC caused a significant decrease in GSH contents in SCLC cells, which was followed by increase in the formation of reactive oxygen species. Depletion of GSH due to L-buthionine sulfoximine enhanced the MMC-induced activation of caspase-3 and cell death in SCLC cells. Antioxidants, including N-acetylcysteine, depressed formations of nitric oxide, malondialdehyde and carbonyls due to MMC in SCLC cells. The results show that the reductive activation of MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to caspase-3 activation, and by activation of caspase-8. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by decrease in the intracellular GSH contents due to oxidative attack of free radicals. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/15450951/Effect_of_change_in_cellular_GSH_levels_on_mitochondrial_damage_and_cell_viability_loss_due_to_mitomycin_c_in_small_cell_lung_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(04)00426-5 DB - PRIME DP - Unbound Medicine ER -