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TRAIL in Combination with Subtoxic 5-FU Effectively Inhibit Cell Proliferation and Induce Apoptosis in Cholangiocarcinoma Cells
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 Title & Authors
TRAIL in Combination with Subtoxic 5-FU Effectively Inhibit Cell Proliferation and Induce Apoptosis in Cholangiocarcinoma Cells
Sriraksa, Ruethairat; Limpaiboon, Temduang;
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In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.
Novel cancer therapy;TRAIL/Apo2L;non-conventional anti-cancer therapy;apoptosis;
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Ashkenazi A, Pai R, Fong S, et al (1999). Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest, 104, 155-62. crossref(new window)

Bhudhisawasdi V, Talabnin C, Pugkhem A, et al (2012). Evaluation of postoperative adjuvant chemotherapy for intrahepatic cholangiocarcinoma patients undergoing R1 and R2 resections. Asian Pac J Cancer Prev, 13, 169-74 crossref(new window)

Huang Y, Sheikh MS (2007). TRAIL death receptors and cancer therapeutics. Toxicol Appl Pharmacol, 224, 284-9. crossref(new window)

Jane EP, Premkumar DR, Pollack IF (2011). Bortezomib sensitizes malignant human glioma cells to TRAIL, mediated by inhibition of the NF-{kappa}B signaling pathway. Mol Cancer Ther, 10, 198-208. crossref(new window)

Keane MM, Ettenberg SA, Nau MM, Russell EK, Lipkowitz S (1999). Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res, 59, 734-41.

Khan SA, Davidson BR, Goldin R, et al (2002). Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut, 51, 7-9. crossref(new window)

Khan SA, Thomas HC, Davidson BR, et al (2005). Cholangiocarcinoma. Lancet, 366, 1303-14. crossref(new window)

Kiba T, Tsuda H, Pairojkul C, et al (1993). Mutations of the p53 tumor suppressor gene and the ras gene family in intrahepatic cholangiocellular carcinomas in Japan and Thailand. Mol Carcinog, 8, 312-8. crossref(new window)

Kim K, Fisher MJ, Xu SQ, el-Deiry WS (2000). Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res, 6, 335-46.

Kruyt FA (2008). TRAIL and cancer therapy. Cancer Lett, 263, 4-25.

Lee MA, Woo IS, Kang JH, Hong YS, Lee KS (2004). Epirubicin, cisplatin, and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma. J Cancer Res Clin Oncol, 130, 346-50. crossref(new window)

Limpaiboon T, Krissadarak K, Sripa B, et al (2002). Microsatellite alterations in liver fluke related cholangiocarcinoma are associated with poor prognosis. Cancer Lett, 181, 215-22. crossref(new window)

Mahmood Z, Shukla Y (2010). Death receptors: targets for cancer therapy. Exp Cell Res, 316, 887-99. crossref(new window)

Martin R, Jarnagin W (2003). Intrahepatic cholangiocarcinoma. Current Management. Minerva Chir, 58, 469-78.

Merino D, Lalaoui N, Morizot A, et al (2006). Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol, 26, 7046-55. crossref(new window)

Morise Z, Sugioka A, Tokoro T, et al (2010). Surgery and chemotherapy for intrahepatic cholangiocarcinoma. World J Hepatol, 2, 58-64.

Mosconi S, Beretta G, Labianca R, et al (2009). Cholangiocarcinoma. Crit Rev Oncol Hematol, 69, 259-70. crossref(new window)

Oya M, Ohtsubo M, Takayanagi A, et al (2001). Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells. Oncogene, 20, 3888-96. crossref(new window)

Panichakul T, Intachote P, Wongkajorsilp A, Sripa B, Sirisinha S (2006). Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis. Anticancer Res, 26, 259-65.

Patel T (2001). Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology, 33, 1353-7. crossref(new window)

Patt YZ, Hassan MM, Lozano RD, et al (2001). Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer. Clin Cancer Res, 7, 3375-80.

Petak I, Douglas L, Tillman DM, Vernes R, Houghton JA (2000). Pediatric rhabdomyosarcoma cell lines are resistant to Fasinduced apoptosis and highly sensitive to TRAIL-induced apoptosis. Clin Cancer Res, 6, 4119-27.

Pitti RM, Marsters SA, Ruppert S, et al (1996). Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor receptor family. J Biol Chem, 271, 12687-90. crossref(new window)

Sanlioglu AD, Dirice E, Aydin C, et al (2005). Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells. BMC Cancer, 5, 54. crossref(new window)

Shaib YH, Davila JA, McGlynn K, El-Serag HB (2004). Rising incidence of intrahepatic cholangiocarcinoma in the United States: A true increase? J Hepatol, 40, 472-7. crossref(new window)

Shaib Y, El-Serag HB (2004). The epidemiology of cholangiocarcinoma. Semin Liver Dis, 24,115-25. crossref(new window)

Shin HR, Oh JK, Masuyer E, et al (2010). Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma--focus on East and South-Eastern Asia. Asian Pac J Cancer Prev, 11, 1159-66.

Sriraksa R, Limpaiboon T (2013). Histone deacetylases and their Inhibitors as potential therapeutic drugs for cholangiocarcinoma-Cell line findings. Asian Pac J Cancer Prev, 14, 2503-8. crossref(new window)

Sriraksa R, Zeller C, El-Bahrawy MA, et al (2011). CpG-island methylation study of liver fluke-related cholangiocarcinoma. Br J Cancer, 104, 1313-8. crossref(new window)

Taniai M, Grambihler A, Higuchi H, et al (2004). Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in human cholangiocarcinoma cells. Cancer Res, 64, 3517-24. crossref(new window)

Taylor-Robinson SD, Toledano MB, et al (2001). Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968-1998. Gut, 48, 816-20. crossref(new window)

Thongprasert S (2005). The role of chemotherapy in cholangiocarcinoma. Ann Oncol, 16, 93-6.

Vichai V, Kirtikara K (2006). Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc, 1, 1112-6. crossref(new window)

Walczak H, Miller RE, Ariail K, et al (1999). Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligandin vivo. Nat Med, 5, 157-63. crossref(new window)

Wiley SR, Schooley K, Smolak PJ, et al (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity, 3, 673-82. crossref(new window)