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Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs.
Free Radic Biol Med. 2007 Oct 15; 43(8):1197-207.FR

Abstract

Tumor necrosis factor-alpha (TNF-alpha) and several anticancer drugs induce the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In the present report, we show that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by TNF-alpha and anticancer drugs. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of anticancer agent-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy.

Authors+Show Affiliations

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.No 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

17854715

Citation

Kil, In Sup, et al. "Small Interfering RNA-mediated Silencing of Mitochondrial NADP+-dependent Isocitrate Dehydrogenase Enhances the Sensitivity of HeLa Cells Toward Tumor Necrosis Factor-alpha and Anticancer Drugs." Free Radical Biology & Medicine, vol. 43, no. 8, 2007, pp. 1197-207.
Kil IS, Kim SY, Lee SJ, et al. Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. Free Radic Biol Med. 2007;43(8):1197-207.
Kil, I. S., Kim, S. Y., Lee, S. J., & Park, J. W. (2007). Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. Free Radical Biology & Medicine, 43(8), 1197-207.
Kil IS, et al. Small Interfering RNA-mediated Silencing of Mitochondrial NADP+-dependent Isocitrate Dehydrogenase Enhances the Sensitivity of HeLa Cells Toward Tumor Necrosis Factor-alpha and Anticancer Drugs. Free Radic Biol Med. 2007 Oct 15;43(8):1197-207. PubMed PMID: 17854715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. AU - Kil,In Sup, AU - Kim,Sung Youl, AU - Lee,Sun Joo, AU - Park,Jeen-Woo, Y1 - 2007/07/20/ PY - 2007/03/28/received PY - 2007/07/10/revised PY - 2007/07/14/accepted PY - 2007/9/15/pubmed PY - 2007/12/21/medline PY - 2007/9/15/entrez SP - 1197 EP - 207 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 43 IS - 8 N2 - Tumor necrosis factor-alpha (TNF-alpha) and several anticancer drugs induce the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In the present report, we show that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by TNF-alpha and anticancer drugs. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of anticancer agent-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/17854715/Small_interfering_RNA_mediated_silencing_of_mitochondrial_NADP+_dependent_isocitrate_dehydrogenase_enhances_the_sensitivity_of_HeLa_cells_toward_tumor_necrosis_factor_alpha_and_anticancer_drugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(07)00490-X DB - PRIME DP - Unbound Medicine ER -