Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer

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• 作者：Junran Xie (1) (2) (3)
  Yaping Zhang (2) (3)
  Xuming Hu (2) (3)
  Ran Lv (1)
  Dongju Xiao (2) (3)
  Li Jiang (1)
  Qi Bao (1)
  
  1. Department of Anesthesiology ; Sir Run Run Shaw Hospital ; Zhejiang University School of Medicine ; 3 Eastern Qingchun Road ; Hangzhou ; 310016 ; People鈥檚 Republic of China
  2. Jiangsu Province Key Laboratory of Anesthesiology ; Xuzhou Medical College ; Xuzhou ; People鈥檚 Republic of China
  3. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology ; Xuzhou ; People鈥檚 Republic of China
  
• 关键词：Norcantharidin ; Wnt signal pathway ; Wnt inhibitory factor ; 1 ; Demethylation ; Non ; small cell lung cancer
• 刊名：Medical Oncology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：32
• 期：5
• 全文大小：3,004 KB
• 参考文献：1. Luan, J, Duan, H, Liu, Q, Yagasaki, K, Zhang, G (2010) Inhibitory effects of norcantharidin against human lung cancer cell growth and migration. Cytotechnology 62: pp. 349-355 CrossRef
  2. Stewart, DJ, Chang, DW, Ye, Y, Spitz, M, Lu, C, Shu, X, Wampfler, JA, Marks, RS, Garces, YI, Yang, P, Wu, X (2014) Wnt signaling pathway pharmacogenetics in non-small cell lung cancer. Pharmacogenomics J 14: pp. 509-522 CrossRef
  3. Mazieres, J, He, B, You, L, Xu, ZD, Jablons, DA (2005) Wnt signaling in lung cancer. Cancer Lett 222: pp. 1-10 CrossRef
  4. Gao, Z, Xu, Z, Hung, MS, Lin, YC, Wang, T, Gong, M, Zhi, X, Jablons, DM, You, L (2009) Procaine and procainamide inhibit the Wnt canonical pathway by promoter demethylation of WIF-1 in lung cancer cells. Oncol Rep 22: pp. 1479-1484
  5. Chen, X, Hu, W, Xie, B, Gao, H, Xu, C, Chen, J (2014) Downregulation of SCAI enhances glioma cell invasion and stem cell like phenotype by activating Wnt/尾-catenin signaling. Biochem Biophys Res Commun 448: pp. 206-211 CrossRef
  6. Schneider, AJ, Branam, AM, Peterson, RE (2014) Intersection of AHR and Wnt signaling in development, health, and disease. Int J Mol Sci 15: pp. 17852-17885 CrossRef
  7. Kim, SA, Kwak, J, Nam, HY, Chun, SM, Lee, BW, Lee, HJ, Khang, SK, Kim, SW (2013) Promoter methylation of Wnt inhibitory factor-1 and expression pattern of Wnt/尾-catenin pathway in human astrocytoma: pathologic and prognostic correlations. Mod Pathol 26: pp. 626-639 CrossRef
  8. Wu, J, Fang, J, Yang, Z, Chen, F, Liu, J, Wang, Y (2012) Wnt inhibitory factor-1 regulates glioblastoma cell cycle and proliferation. J Clin Neurosci 19: pp. 1428-1432 CrossRef
  9. Yang, Z, Wang, Y, Fang, J, Chen, F, Liu, J, Wu, J, Wang, Y (2010) Expression and aberrant promoter methylation of Wnt inhibitory factor-1 in human astrocytomas. J Exp Clin Cancer Res 29: pp. 26 CrossRef
  10. Liu, D, Shi, P, Yin, X, Chen, Z, Zhang, X (2012) Effect of norcantharidin on the human breast cancer Bcap-37 cells. Connect Tissue Res 53: pp. 508-512 CrossRef
  11. Jiang, YM, Meng, ZZ, Yue, GX, Chen, JX (2012) Norcantharidin induces HL-60 cells apoptosis in vitro. Evid-Based Complement Alternat Med 2012: pp. 154271
  12. Liao, HF, Chen, YJ, Chou, CH, Wang, FW, Kuo, CD (2011) Norcantharidin induces cell cycle arrest and inhibits progression of human leukemic Jurkat T cells through mitogen-activated protein kinase-mediated regulation of interleukin-2 production. Toxicol In Vitro 25: pp. 206-212 CrossRef
  13. Liu, S, Yu, H, Kumar, SM, Martin, JS, Bing, Z, Sheng, W, Bosenberg, M, Xu, X (2011) Norcantharidin induces melanoma cell apoptosis through activation of TR3 dependent pathway. Cancer Biol Ther 12: pp. 1005-1014 CrossRef
  14. Mazieres, J, He, B, You, L, Xu, Z, Lee, AY, Mikami, I, Reguart, N, Rosell, R, McCormick, F, Jablons, DM (2004) Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res 64: pp. 4717-4720 CrossRef
  15. Feng, PH, Yu, CT, Wu, CY, Lee, MJ, Lee, WH, Wang, LS, Lin, SM, Fu, JF, Lee, KY, Yen, TH (2014) Tumor-associated macrophages in stage IIIa pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery. Am J Transl Res 6: pp. 593-603
  16. Faria, SL (2014) Role of radiotherapy in metastatic non-small cell lung cancer. Front Oncol 4: pp. 229 CrossRef
  17. D鈥橝ntonio, C, Milano, A, Righini, R, Onesti, CE, Bassanelli, M, Falcone, R, Paris, I, Lauro, S, Marchetti, P (2014) Pharmacogenomics in lung cancer chemotherapy: a review of what the oncologist should know. Anticancer Res 34: pp. 5241-5250
  18. Mellemgaard, A, Luchtenborg, M, Iachina, M, Jakobsen, E, Green, A, Krasnik, M, Moller, H (2015) Role of comorbidity on survival after radiotherapy and chemotherapy for nonsurgically treated lung cancer. J Thorac Oncol 10: pp. 272-279 CrossRef
  19. Mostafa, AA, Morris, DG (2014) Immunotherapy for lung cancer: has it finally arrived?. Front Oncol 4: pp. 288 CrossRef
  20. Rosell, R, Gomez-Codina, J, Camps, C, Maestre, J, Padille, J, Canto, A, Mate, JL, Li, S, Roig, J, Olazabal, A (1994) A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 330: pp. 153-158 CrossRef
  21. Andre, F, Grunenwald, D, Pignon, JP, Dujon, A, Pujol, JL, Brichon, PY, Brouchet, L, Quoix, E, Westeel, V, Chevalier, T (2000) Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 18: pp. 2981-2989
  22. Shou, LM, Zhang, QY, Li, W, Xie, X, Chen, K, Lian, L, Li, ZY, Gong, FR, Dai, KS, Mao, YX, Tao, M (2013) Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of 伪2 integrin. Oncol Rep 30: pp. 1059-1066
  23. Clevers, H, Loh, KM, Nusse, R (2014) Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346: pp. 1248012 CrossRef
  24. Schule, R, Dictus, C, Campos, B, Wan, F, Felsberg, J, Ahmadi, R, Centner, FS, Grabe, N, Reifenberger, G, Bermejo, JL, Unterberg, A, Herold-Mende, C (2012) Potential canonical Wnt pathway activation in high-grade astrocytomas. ScientificWorldJournal 2012: pp. 697313 CrossRef
  25. Bilir, B, Kucuk, O, Moreno, CS (2013) Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J Transl Med 11: pp. 280 CrossRef
  26. Wu, MY, Xie, X, Xu, ZK, Xie, L, Chen, Z, Shou, LM, Gong, FR, Xie, YF, Li, W, Tao, M (2014) PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells through inhibition on the Wnt/尾-catenin pathway by phosphorylation and degradation of 尾-catenin. Oncol Rep 32: pp. 513-522
  27. Tan, M, Wu, J, Cai, Y (2013) Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer. Biochem Biophys Res Commun 438: pp. 673-679 CrossRef
  28. Jamieson, C, Sharma, M, Henderson, BR (2014) Targeting the 尾-catenin nuclear transport pathway in cancer. Semin Cancer Biol 27: pp. 20-29 CrossRef
  29. Zhang, JT, Sun, W, Zhang, WZ, Ge, CY, Liu, ZY, Zhao, ZM, Lu, XS, Fan, YZ (2014) Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5纬2 signaling pathway. BMC Cancer 14: pp. 193 CrossRef
  30. Chen, YJ, Tsai, YM, Kuo, CD, Ku, KL, Shie, HS, Liao, HF (2009) Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect. Life Sci 85: pp. 642-651 CrossRef
  31. Yu, CC, Ko, FY, Yu, CS, Lin, CC, Huang, YP, Yang, JS, Lin, JP, Chung, JG (2012) Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells. Int J Oncol 41: pp. 1050-1060
  32. Shen, B, He, PJ, Shao, CL (2013) Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion. PLoS One 8: pp. e84610 CrossRef
  33. Chen, YN, Chen, JC, Yin, SC, Wang, GS, Tsauer, W, Hsu, SF, Hsu, SL (2002) Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells. Int J Cancer 100: pp. 158-165 CrossRef
  34. Hill, TA, Stewart, SG, Ackland, SP, Gilbert, J, Sauer, B, Sakoff, JA, McCluskey, A (2007) Norcantharimides, synthesis and anticancer activity: synthesis of new norcantharidin analogues and their anticancer evaluation. Bioorg Med Chem 15: pp. 6126-6134 CrossRef
  35. Fan, YZ, Fu, JY, Zhao, ZM, Chen, CQ (2007) Inhibitory effect of norcantharidin on the growth of human gallbladder carcinoma GBC-SD cells in vitro. Hepatobiliary Pancreat Dis Int 6: pp. 72-80
  36. Chen, YJ, Shieh, CJ, Tsai, TH, Kuo, CD, Ho, LT, Liu, TY, Liao, HF (2005) Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells. Anticancer Drugs 16: pp. 293-299 CrossRef
  37. Lee, YC, Lee, LM, Yang, CH, Lin, AM, Huang, YC, Hsu, CC, Chen, MS, Chi, CW, Yin, PH, Kuo, CD, Liao, JF, Lee, HC (2013) Norcantharidin suppresses cell growth and migration with enhanced anticancer activity of gefitinib and cisplatin in human non-small cell lung cancer cells. Oncol Rep 29: pp. 237-243
  38. Peng, F, Wei, YQ, Tian, L, Yang, L, Zhao, X, Lu, Y, Mao, YQ, Kan, B, Lei, S, Wang, GS, Jiang, Y, Wang, QR, Luo, F, Zou, LQ, Liu, JY (2002) Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand. J Cancer Res Clin Oncol 128: pp. 223-230 CrossRef
  39. Liao, HF, Su, SL, Chen, YJ, Chou, CH, Kuo, CD (2007) Norcantharidin preferentially induces apoptosis in human leukemic Jurkat cells without affecting viability of normal blood mononuclear cells. Food Chem Toxicol 45: pp. 1678-1687 CrossRef
  40. An, WW, Gong, XF, Wang, MW, Tashiro, S, Onodera, S, Ikejima, T (2004) Norcantharidin induces apoptosis in HeLa cells through caspase, MAPK, and mitochondrial pathways. Acta Pharmacol Sin 25: pp. 1502-1508
  41. Zhang, L, Ji, Q, Liu, X, Chen, X, Chen, Z, Qiu, Y, Sun, J, Cai, J, Zhu, H, Li, Q (2013) Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK signaling pathways. Cancer Sci 104: pp. 604-610 CrossRef
  
• 刊物主题：Oncology; Hematology; Pathology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-131X

文摘

Wingless-type (Wnt) family of secreted glycoproteins is a group of signal molecules implicated in oncogenesis. Abnormal activation of Wnt signal pathway is associated with a variety of human cancers, including non-small cell lung cancer (NSCLC). Wnt antagonists, such as the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, inhibit Wnt signal pathway by directly binding to Wnt molecules. Norcantharidin (NCTD) is known to possess anticancer activity but less nephrotoxicity than cantharidin. In this study, we found that NCTD inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. NCTD treatment blocked cytoplasmic translocation of beta-catenin into the nucleus. Alterations of apoptosis-related proteins, such as Bax, cleaved caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic), had been detected. Furthermore, the expression levels of WIF-1 and SFRP1 were significantly increased in NCTD-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while NCTD treatment promoted WIF-1 demethylation. The present study revealed that NCTD activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo.