Browse > Article
http://dx.doi.org/10.3857/jkstro.2010.28.2.91

The Effect of Troglitazone on Thermal Sensitivity in Uterine Cervix Cancer Cells  

Lee, Ji-Hye (Department of Radiation Oncology, Chungbuk National University College of Medicine)
Kim, Won-Dong (Department of Radiation Oncology, Chungbuk National University College of Medicine)
Yu, Jae-Ran (Department of Environmental and Tropical Medicine, Konkuk University College of Medicine)
Park, Woo-Yoon (Department of Radiation Oncology, Chungbuk National University College of Medicine)
Publication Information
Radiation Oncology Journal / v.28, no.2, 2010 , pp. 91-98 More about this Journal
Abstract
Purpose: Troglitazone (TRO), a PPAR-$\gamma$ agonist, can reduce heat shock protein (HSP) 70 and increase the antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, which might affect thermal sensitivity. Here, we investigated whether TRO modifies thermal sensitivity in uterine cervical cancer cells, which is most commonly treated by hyperthermia (HT). Materials and Methods: HeLa cells were treated with $5{\mu}M$ TRO for 24 hours before HT at $42^{\circ}C$ for 1 hour. Cell survival was analyzed by clonogenic assay. The expression of HSPs was analyzed by Western blot. SOD and catalase activity was measured and reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate and dihydroethidium. Results: The decreased cell survival by HT was increased by preincubation with TRO before HT. Expression of HSP 70 was increased by HT however, it was not decreased by preincubation with TRO before HT. The decreased Bcl-2 expression by HT was increased by preincubation with TRO. SOD and catalase activity was increased by 1.2 and 1.3 times,respectively with TRO. Increased ROS by HT was decreased by preincubation with TRO. Conclusion: TRO decreases thermal sensitivity through increased SOD and catalase activity, as well as scavenging ROS in HeLa cells.
Keywords
Troglitazone; Hyperthermia; Reactive oxygen species;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Li GC, Mivechi NF, Weitzel G. Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia. Int J Hyperthermia 1995;11:459-488   DOI   ScienceOn
2 Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol 1995;11:441-469   DOI   ScienceOn
3 Kregel KC. Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 2002;92:2177-2186
4 Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006;20:207-225   DOI   ScienceOn
5 Song CW, Park HJ, Lee CK, Griffin R. Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment. Int J Hyperthermia 2005;21:761-767   DOI   ScienceOn
6 Vasanthan A, Mitsumori M, Park JH, et al. Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency. Int J Radiat Oncol Biol Phys 2005;61:145-153   DOI   ScienceOn
7 Franckena M, Lutgens LC, Koper PC, et al. Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients. Int J Radiat Oncol Biol Phys 2009;73:242-250   DOI   ScienceOn
8 van der Zee J, Gonzalez Gonzalez D, van Rhoon GC, van Dijk JD, van Putten WL, Hart AA. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Lancet 2000;355:1119-1125
9 Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 2002;43:33-56   DOI   ScienceOn
10 Dewey WC, Hopwood LE, Sapareto SA, Gerweck LE. Cellular responses to combinations of hyperthermia and radiation. Radiology 1977;123:463-474   DOI
11 Choi DH, Kim ES, Kim YH, et al. Literature analysis of radiotherapy in uterine cervix cancer for the processing of the patterns of care study in Korea. J Korean Soc Ther Radiol Oncol 2005;23:61-70   과학기술학회마을
12 Girnun GD, Domann FE, Moore SA, Robbins ME. Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol Endocrinol 2002;16:2793-2801   DOI   ScienceOn
13 Gorman AM, Heavey B, Creagh E, Cotter TG, Samali A. Antioxidant-mediated inhibition of the heat shock response leads to apoptosis. FEBS Lett 1999;445:98-102   DOI   ScienceOn
14 He L, Lemasters JJ. Heat shock suppresses the permeability transition in rat liver mitochondria. J Biol Chem 2003;278:16755-16760   DOI   ScienceOn
15 Beere HM, Wolf BB, Cain K, et al. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2000;2:469-475   DOI   ScienceOn
16 Xu Y, Lu L, Greyson C, et al. Deleterious effects of acute treatment with a peroxisome proliferator-activated receptorgamma activator in myocardial ischemia and reperfusion in pigs. Diabetes 2003;52:1187-1194   DOI   ScienceOn
17 Bruey JM, Ducasse C, Bonniaud P, et al. Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol 2000;2:645-652   DOI   ScienceOn
18 Inoue I, Goto S, Matsunaga T, et al. The ligands/ activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+, Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism 2001;50:3-11   DOI   ScienceOn
19 Welbourne T, Su G, Coates G, Routh R, McCarthy K, Battarbee H. Troglitazone induces a cellular acidosis by inhibiting acid extrusion in cultured rat mesangial cells. Am J Physiol Regul Integr Comp Physiol 2002;282:R1600-R1607
20 Koeffler HP. Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res 2003;9:1-9
21 Wu L, Eftekharpour E, Davies GF, Roesler WJ, Juurlink BH. Troglitazone selectively inhibits glyoxalase I gene expression. Diabetologia 2001;44:2004-2012   DOI   ScienceOn
22 Arya R, Mallik M, Lakhotia SC. Heat shock genes: integrating cell survival and death. J Biosci 2007;32:595-610   DOI   ScienceOn
23 Davies GF, Khandelwal RL, Wu L, Juurlink BH, Roesler WJ. Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by troglitazone: a peroxisome proliferator-activated receptor-gamma (PPARgamma)-independent, antioxidant-related mechanism. Biochem Pharmacol 2001; 62:1071-1079   DOI   ScienceOn
24 Inoue I, Katayama S, Takahashi K, et al. Troglitazone has a scavenging effect on reactive oxygen species. Biochem Biophys Res Commun 1997;235:113-116   DOI   ScienceOn
25 Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 2002;3:214-220   DOI   ScienceOn
26 Davies GF, Roesler WJ, Ovsenek N, Bharadwaj LA. Troglitazone reduces heat shock protein 70 content in primary rat hepatocytes by a ubiquitin proteasome independent mechanism. Pharmacol Res 2003;48:119-126
27 Campbell MJ, Carlberg C, Koeffler HP. A role for the PPARgamma in cancer therapy. PPAR Res 2008;2008:314974
28 Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996;45: 1661-1669   DOI   ScienceOn
29 Rossi A, Ciafre S, Balsamo M, Pierimarchi P, Santoro MG. Targeting the heat shock factor 1 by RNA interference: a potent tool to enhance hyperthermochemotherapy efficacy in cervical cancer. Cancer Res 2006;66:7678-7685   DOI   ScienceOn
30 Calderwood SK, Asea A. Targeting HSP70-induced thermotolerance for design of thermal sensitizers. Int J Hyperthermia 2002;18:597-608   DOI   ScienceOn
31 Jung TI, Baek WK, Suh SI, et al. Down-regulation of peroxisome proliferator-activated receptor gamma in human cervical carcinoma. Gynecol Oncol 2005;97:365-373   DOI   ScienceOn
32 Boonstra J, Post JA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 2004;337:1-13   DOI   ScienceOn
33 Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000;408:239-247   DOI   ScienceOn
34 Zhao QL, Fujiwara Y, Kondo T. Mechanism of cell death induction by nitroxide and hyperthermia. Free Radic Biol Med 2006;40:1131-1143   DOI   ScienceOn
35 Friday E, Oliver R 3rd, Welbourne T, Turturro F. Role of epidermal growth factor receptor (EGFR)-signaling versus cellular acidosis via Na+/H+ exchanger1(NHE1)-inhibition in troglitazone-induced growth arrest of breast cancer-derived cells MCF-7. Cell Physiol Biochem 2007;20:751-762   DOI   ScienceOn
36 Katschinski DM, Boos K, Schindler SG, Fandrey J. Pivotal role of reactive oxygen species as intracellular mediators of hyperthermia-induced apoptosis. J Biol Chem 2000;275:21094-21098   DOI   ScienceOn