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Inducing Apoptosis of NCI-H157 Human Lung Carcinoma Cells via Activation of Caspase Cascade by Combination Treatment with Arsenic Trioxide and Sulindac  

Kim, Hak Ryul (Department of Internal Medicine, College of Medicine Wonkwang University)
Yang, Sei Hoon (Department of Internal Medicine, College of Medicine Wonkwang University)
Jeong, Eun Taik (Department of Internal Medicine, College of Medicine Wonkwang University)
Publication Information
Tuberculosis and Respiratory Diseases / v.56, no.4, 2004 , pp. 381-392 More about this Journal
Abstract
Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.
Keywords
Arsenic trioxide; Sulindac; Apoptosis; Lung Cancer Cell line;
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1 Zhang TC, Cao EH, Li JF, Ma W, Qin JF. Induction of apoptosis and inhibition of hu man gastric cancer MGC-803 cell growth by arsenic trioxide. Eur J Cancer 1999;35:1258- 63
2 Smalley WE, Dubois RN. Colorectal cancer and non-steroidal anti-inflammatory drugs. Adv Pharmacol 1997;39:1-20
3 Klampfer L, Cammenga J, Wisniewski HG, Nimer SD. Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood 1999;93:2386-94
4 Williams GT. Apoptosis in the immune system. J Pathol 1994;173:1-4
5 Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, et al. In vitro studies on molecular mechanisms of arsenic trioxide in the treatment of acute promyelocytic leu kemia: arsenic trioxide induces NB4 cell apoptosis with downregualation of Bcl-2 expression and modulation of PML-RARα /PML proteins. Blood 1996;88:1052-61
6 Ling YH, Jiang JD, Holland JF, Perez-Soler R. Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines. Mol Pharmacol 2002;62:529-38
7 Shiff SJ, Qiao L, Tsai LL, Rigas B. Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adeno carcinoma cells. J Clin Invest 1995;96:491-503
8 Huang S, Huang CF, Lee T. Induction of mitosis-mediated apoptosis by sodium arse nite in Hela S3 cells. Biochem Pharmacol 2000;60:771-80
9 Chen CJ, Chen CW, Wu MM, Kuo TL. Cancer potential in liver, lung, bladder andkidney due to ingested inorganic arsenic in drinking water. Br J Cancer 1992;66:888-92
10 Chen CJ, Wu MM, Lee SS, Wang JD, Cheng SH, Wu HY. Atherogenicity and carcino genecity of high-arsenicartesian well water: Multiple risk factors and related malignant neoplasm of blackfoot disease. Arterio sclerosis 1988;8:452-60
11 Park WH, Seol JG, Kim ES, Hyun JM, Jung CW, Lee CC, et al. Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res 2000;60:3065-71
12 Jung BH, Park C, Kim HR, Park MR. Arse nic trioxide induces apoptosis of HL-60 cells via activation of intrinsic caspase protease with mitochondrial dysfunction. Cancer Res and Treat 2002;34:308-15
13 Seol JG, Park WH, Kim ES, Jung CW, Hyun JM, Kim BK, et al. Effect of arsenic trioxide on cell cycle arrest in head and neck cancercell line PCI-1. Biochem Biophys Res Commun 1999;265:400-4
14 Soriano AF, Helfrich B, Chan DC, Heasley LE, Bunn PA Jr, Chou TC et al. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res 1999;59: 6178-84
15 Harris RE, Nambodiri KK, Farrar WB. Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 1996;7:203-5
16 Duffy CP, Elliott CJ, O'Connor RA, Heenan MM, Coyle S, Cleary IM, et al. Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of NSAIDs. Eur J Cancer 1998;34:1250-9
17 Zheng J, Deng YP, Lin C, Fu M, Xiao PG, Wu M. Arsenic trioxide incuces apoptosis of HPV16 DNA-immortalized human cervical epithelial cells and selectively inhibits viral gene expression. Int J Cancer 1999;82:286-92
18 Cohen JJ. Apoptosis: the physiologic pathway of cell death. Hosp Pract 1993;28:35-43
19 Hida T, Kozaki K, Muramatsu H, Masuda A, Shimizu S, Mitsudomi T, et al. Cyclooxy genase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell ines. Clin Cancer Res 2000;6:2006-11
20 Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, et al. Use of arsenic trioxide(As2O3) in the treatment of acute promye lcytic leukemia(APL): I. As2O3 exerts dosedependent dual effects on APL cells. Blood 1997;89:3345-53
21 Torrance CJ, Jackson PE, Montgomery E, Kinzler KW, Vogelstein B, Wissner A, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000;6:1024-8
22 Dannenberg AJ, Zakim D. Chemoprevention of colon-rectal cancer through inhibition of cyclooxygenase-2. Semin Oncol 1999;26:499-504
23 Sun HD, Ma L, Hu XC, Zhang TD. Treatment of acute promyelocytic leukemiaby Ailing-1 therapy with use of syndrome differentiation of traditional Chinese medicine. Chin J Comb Trad Chin Med West Med 1992;12:170-1
24 Koki AT, Leahy KM, Masferrer JL. Potential utility of COX-2 inhibitors in chemopre vention and chemotherapy. Expert Opin In vest Drugs 1999;8:1623-38
25 Uslu R, Sanli UA, Sezgin C, Karabulut B, Terzioglu E, Omay SB, et al. Arsenic trio xide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines. Clin Cancer Res 2000;6:4957-64
26 Shen ZY, Tan LJ, Cai WJ, Shen J, Chen C, Tang XM, et al. Arsenic trioxide induces apoptosis of oesophageal carcinoma in vitro. Int J Mol Med 1999;4:33
27 Chan TA, Morin PJ, Vogelstein B, Kinzler KW. Mechanism underlying nonsteroidal antiinflammatory drug-mediated apoptosis. Proc Natl Acad Sci 1998;95:681-6
28 Milas L. Cyclooxygenase-2 (COX-2) enzyme inhibitors as potential enhancers of tumor radioresponse. Semin Radiat Oncol 2001;11: 290-9
29 Milas L, Kishi K, Hunter N, Mason K, Masferrer JL, Tofilon PJ. Enhancement oftumor response to gamma-radiation by an inhibitor of cyclooxygenase-2 enzyme. J Natl Cancer Inst 1999;91:1501-4
30 Thun MJ, Namboodiri NM, Health CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 1991;325:1593-6
31 Akao Y, Nakagawa Y, Akiyama K. Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro. FEBS Lett 1992;445:59-62
32 Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001;19:3852-60
33 Scheinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer inci dence in a prospective study. Epidemiology 1994;5:138-46