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http://dx.doi.org/10.4196/kjpp.2017.21.4.397

MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through CHOP-mediated DR5 upregulation  

Lim, Sung-Chul (Department of Pathology, College of Medicine, Chosun University)
Han, Song Iy (Division of Premedical Science, College of Medicine, Chosun University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.21, no.4, 2017 , pp. 397-405 More about this Journal
Abstract
MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (${\sim}20{\mu}M$), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than $20{\mu}M$, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.
Keywords
Apoptosis; CHOP; DR5; Gastric cancer; MDL-12330A; TRAIL;
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1 Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999;83:18-29.
2 Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51:15-36.   DOI
3 Roukos DH. Current status and future perspectives in gastric cancer management. Cancer Treat Rev. 2000;26:243-255.   DOI
4 Gura T. How TRAIL kills cancer cells, but not normal cells. Science. 1997;277:768.   DOI
5 Baker SJ, Reddy EP. Modulation of life and death by the TNF receptor superfamily. Oncogene. 1998;17:3261-3270.   DOI
6 Ashkenazi A. Targeting death and decoy receptors of the tumournecrosis factor superfamily. Nat Rev Cancer. 2002;2:420-430.   DOI
7 Srivastava RK. TRAIL/Apo-2L: mechanisms and clinical applications in cancer. Neoplasia. 2001;3:535-546.   DOI
8 Prasad S, Yadav VR, Kannappan R, Aggarwal BB. Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors: evidence for the role of reactive oxygen species and JNK. J Biol Chem. 2011;286:5546-5557.   DOI
9 Siddiqui IA, Malik A, Adhami VM, Asim M, Hafeez BB, Sarfaraz S, Mukhtar H. Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008;27:2055-2063.   DOI
10 Szliszka E, Krol W. The role of dietary polyphenols in tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis for cancer chemoprevention. Eur J Cancer Prev. 2011;20:63-69.   DOI
11 Seifert R, Lushington GH, Mou TC, Gille A, Sprang SR. Inhibitors of membranous adenylyl cyclases. Trends Pharmacol Sci. 2012;33:64-78.   DOI
12 Li X, Guo Q, Gao J, Yang J, Zhang W, Liang Y, Wu D, Liu Y, Weng J, Li Q, Zhang Y. The adenylyl cyclase inhibitor MDL-12,330A potentiates insulin secretion via blockade of voltage-dependent K(+) channels in pancreatic beta cells. PLoS One. 2013;8:e77934.   DOI
13 Gadea A, Lopez E, Lopez-Colome AM. The adenylate cyclase inhibitor MDL-12330A has a non-specific effect on glycine transport in Muller cells from the retina. Brain Res. 1999;838:200-204.   DOI
14 Pennati M, Sbarra S, De Cesare M, Lopergolo A, Locatelli SL, Campi E, Daidone MG, Carlo-Stella C, Gianni AM, Zaffaroni N. YM155 sensitizes triple-negative breast cancer to membrane-bound TRAIL through p38 MAPK- and CHOP-mediated DR5 upregulation. Int J Cancer. 2015;136:299-309.   DOI
15 Shin JN, Park SY, Cha JH, Park JY, Lee BR, Jung SA, Lee ST, Yun CW, Seol DW, Kim TH. Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases. Exp Cell Res. 2006;312:3892-3898.   DOI
16 Kim CH, Han SI, Lee SY, Youk HS, Moon JY, Duong HQ, Park MJ, Joo YM, Park HG, Kim YJ, Yoo MA, Lim SC, Kang HS. Protein kinase C-ERK1/2 signal pathway switches glucose depletioninduced necrosis to apoptosis by regulating superoxide dismutases and suppressing reactive oxygen species production in A549 lung cancer cells. J Cell Physiol. 2007;211:371-385.   DOI
17 Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006;1:2315-2319.   DOI
18 Kong F, You H, Zhao J, Liu W, Hu L, Luo W, Hu W, Tang R, Zheng K. The enhanced expression of death receptor 5 (DR5) mediated by HBV X protein through NF-kappaB pathway is associated with cell apoptosis induced by (TNF-${\alpha}$ related apoptosis inducing ligand) TRAIL in hepatoma cells. Virol J. 2015;12:192.   DOI
19 Wu GS, Burns TF, McDonald ER 3rd, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS. KILLER/DR5 is a DNA damageinducible p53-regulated death receptor gene. Nat Genet. 1997;17:141-143.   DOI
20 Lim JH, Park JW, Choi KS, Park YB, Kwon TK. Rottlerin induces apoptosis via death receptor 5 (DR5) upregulation through CHOPdependent and PKC delta-independent mechanism in human malignant tumor cells. Carcinogenesis. 2009;30:729-736.   DOI
21 Merino D, Lalaoui N, Morizot A, Solary E, Micheau O. TRAIL in cancer therapy: present and future challenges. Expert Opin Ther Targets. 2007;11:1299-1314.   DOI
22 Fulda S. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Adv Exp Med Biol. 2014;818:167-180.
23 Yoshida T, Shiraishi T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T. Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein. Cancer Res. 2005;65:5662-5667.   DOI
24 Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104:155-162.   DOI
25 Zhou Y, Tian L, Long L, Quan M, Liu F, Cao J. Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. PLoS One. 2013;8:e58855.   DOI
26 Kim S, Lee TJ, Leem J, Choi KS, Park JW, Kwon TK. Sanguinarineinduced apoptosis: generation of ROS, down-regulation of Bcl-2, c-FLIP, and synergy with TRAIL. J Cell Biochem. 2008;104:895-907.   DOI
27 Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T. Tunicamycin enhances tumor necrosis factorrelated apoptosis-inducing ligand-induced apoptosis in human prostate cancer cells. Cancer Res. 2005;65:6364-6370.   DOI
28 English AR, Zurek N, Voeltz GK. Peripheral ER structure and function. Curr Opin Cell Biol. 2009;21:596-602.   DOI
29 Szewczyk A. The intracellular potassium and chloride channels: properties, pharmacology and function (review). Mol Membr Biol. 1998;15:49-58.   DOI
30 Nishitoh H. CHOP is a multifunctional transcription factor in the ER stress response. J Biochem. 2012;151:217-219.   DOI
31 Kuum M, Veksler V, Kaasik A. Potassium fluxes across the endoplasmic reticulum and their role in endoplasmic reticulum calcium homeostasis. Cell Calcium. 2015;58:79-85.   DOI
32 Moon DO, Park SY, Choi YH, Ahn JS, Kim GY. Guggulsterone sensitizes hepatoma cells to TRAIL-induced apoptosis through the induction of CHOP-dependent DR5: involvement of ROSdependent ER-stress. Biochem Pharmacol. 2011;82:1641-1650.   DOI
33 Liu H, Jiang CC, Lavis CJ, Croft A, Dong L, Tseng HY, Yang F, Tay KH, Hersey P, Zhang XD. 2-Deoxy-D-glucose enhances TRAILinduced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2. Mol Cancer. 2009;8:122.   DOI