Browse > Article
http://dx.doi.org/10.5352/JLS.2012.22.10.1277

Inhibition of SIRT1 Sensitizes TRAIL-Resistant MCF-7 Cells by Upregulation of DR5 and Inhibition of c-FLIP  

Lee, Su-Hoon (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Kim, Hak-Bng (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Kim, Mi-Ju (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Lee, Jae-Won (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Bae, Jae-Ho (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Kim, Dong-Wan (Department of Microbiology, College of Natural Sciences, Changwon National University)
Kang, Chi-Dug (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Kim, Sun-Hee (Department of Biochemistry and Medical Research Institute, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.22, no.10, 2012 , pp. 1277-1285 More about this Journal
Abstract
The tumor necrosis, factor-related, apoptosis-inducing ligand (TRAIL) is regarded as a potentially useful anticancer agent with excellent selectivity for cancer cells. However, a considerable number of cancer cells are resistant to apoptosis induction by TRAIL. Developing strategies to overcome this resistance are important for the successful use of TRAIL for cancer therapy. Here, we revealed that siRNA-mediated downregulation of SIRT1 or SIRT1 inhibitor Amurensin G upregulated DR5 and c-Myc and downregulated c-$FLIP_{L/S}$ and Mcl-1, which was associated with sensitization of TRAIL-resistant MCF-7 cells to TRAIL. This result was followed by the activation of caspases, PARP cleavage, and downregulation of Bcl-2 in both TRAIL-treated MCF-7 cells transfected with SIRT1 siRNA and cells co-treated with Amurensin G and TRAIL. Our results suggest that the induction of DR5 and downregulation of c-FLIP via suppression of SIRT1 expression may be a useful strategy to increase the susceptibility of TRAIL-resistant cancer cells to TRAIL-induced cell death.
Keywords
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); SIRT1; c-FLIP; MCF-7 cells; DR5;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Aron, J. L., Parthun, M. R., Marcucci, G., Kitada, S., Mone, A. P., Davis, M. E., Shen, T., Murphy, T., Wickham, J., Kanakry, C., Lucas, D. M., Reed, J. C., Grever, M. R. and Byrd, J. C. 2003. Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood 102, 652-658.   DOI
2 Ashkenazi, A., Pai, R. C., Fong, S., Leung, S., Lawrence, D. A., Marsters, S. A., Blackie, C., Chang, L., McMurtrey, A. E., Hebert, A., DeForge, L., Koumenis, I. L., Lewis, D., Harris, L., Bussiere, J., Koeppen, H., Shahrokh, Z. and Schwall, R. H. 1999. Safety and antitumor activity of recombinant soluble Apo2 ligand. J. Clin. Invest. 104, 155-162.   DOI   ScienceOn
3 Bevis, K. S., Buchsbaum, D. J. and Straughn, J. M., Jr. 2010. Overcoming TRAIL resistance in ovarian carcinoma. Gynecol. Oncol. 119, 157-163.   DOI
4 Bhalla, K. N. 2005. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J. Clin. Oncol. 23, 3971-3993.   DOI
5 Bolden, J. E., Peart, M. J. and Johnstone, R. W. 2006. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769-784.   DOI   ScienceOn
6 Camphausen, K., Scott, T., Sproull, M. and Tofilon, P. J. 2004. Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation. Clin. Cancer Res. 10, 6066-6071.   DOI   ScienceOn
7 Carew, J. S., Giles, F. J. and Nawrocki, S. T. 2008. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 269, 7-17.   DOI
8 Fulda, S. 2008. Modulation of TRAIL-induced apoptosis by HDAC inhibitors. Curr. Cancer Drug Targets 8, 132-140.   DOI   ScienceOn
9 Hall, M. A. and Cleveland, J. L. 2007. Clearing the TRAIL for Cancer Therapy. Cancer Cell 12, 4-6.   DOI
10 Hernandez, A., Thomas, R., Smith, F., Sandberg, J., Kim, S., Chung, D. H. and Evers, B. M. 2001. Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery 130, 265-272.   DOI
11 Kim, H. B., Kim, M. J., Kim, D. Y., Lee, J. W., Bae, J. H., Kim, D. W., Kang, C. D. and Kim, S. H. 2011. High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy- 2-nitrobenzaldehyde. Mol. Cancer 10, 46.   DOI
12 Kim, M. S., Blake, M., Baek, J. H., Kohlhagen, G., Pommier, Y. and Carrier, F. 2003. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 63, 7291-7300.
13 Kruyt, F. A. 2008. TRAIL and cancer therapy. Cancer Lett. 263, 14-25.   DOI
14 Liu, N., Zhang, J., Zhang, J., Liu, S., Liu, Y. and Zheng, D. 2008. Erbin-regulated sensitivity of MCF-7 breast cancer cells to TRAIL via ErbB2/AKT/NF-kappaB pathway. J. Biochem. 143, 793-801.
15 Olmos, Y., Brosens, J. J. and Lam, E. W. 2011. Interplay between SIRT proteins and tumour suppressor transcription factors in chemotherapeutic resistance of cancer. Drug Resist. Updat. 14, 35-44.   DOI
16 Mahajan, S., Dammai, V., Hsu, T. and Kraft, A. S. 2008. Hypoxia-inducible factor-2alpha regulates the expression of TRAIL receptor DR5 in renal cancer cells. Carcinogenesis 29, 1734-1741.   DOI
17 Nieminen, A. I., Partanen, J. I., Hau, A. and Klefstrom, J. 2007. c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis. EMBO J. 26, 1055-1067.   DOI
18 Oh, W. K., Cho, K. B., Hien, T. T., Kim, T. H., Kim, H. S., Dao, T. T., Han, H. K., Kwon, S. M., Ahn, S. G., Yoon, J. H., Kim, T. H., Kim, Y. G. and Kang, K. W. 2010. Amurensin G, a potent natural SIRT1 inhibitor, rescues doxorubicin responsiveness via down-regulation of multidrug resistance 1. Mol. Pharmacol. 78, 855-864.   DOI
19 Park, S. J., Kim, M. J., Kim, H. B., Sohn, H. Y., Bae, J. H., Kang, C. D. and Kim, S. H. 2009. Trichostatin A sensitizes human ovarian cancer cells to TRAIL-induced apoptosis by down-regulation of c-FLIPL via inhibition of EGFR pathway. Biochem. Pharmacol. 77, 1328-1336.   DOI
20 Pathil, A., Armeanu, S., Venturelli, S., Mascagni, P., Weiss, T. S., Gregor, M., Lauer, U. M. and Bitzer, M. 2006. HDAC inhibitor treatment of hepatoma cells induces both TRAIL-independent apoptosis and restoration of sensitivity to TRAIL. Hepatology 43, 425-434.   DOI   ScienceOn
21 Perego, P., Zuco, V., Gatti, L. and Zunino, F. 2012. Sensitization of tumor cells by targeting histone deacetylases. Biochem. Pharmacol. 83, 987-994.   DOI
22 Ricci, M. S., Jin, Z., Dews, M., Yu, D., Thomas-Tikhonenko, A., Dicker, D. T. and El-Deiry, W. S. 2004. Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity. Mol. Cell Biol. 24, 8541-8555.   DOI
23 Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., Ramakrishnan, L., Gray, C. L., Baker, K., Wood, W. I., Goddard, A. D., Godowski, P. and Ashkenazi, A. 1997. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277, 818-821.   DOI   ScienceOn
24 Ricci, M. S., Kim, S. H., Ogi, K., Plastaras, J. P., Ling, J., Wang, W., Jin, Z., Liu, Y. Y., Dicker, D. T., Chiao, P. J., Flaherty, K. T., Smith, C. D. and El-Deiry, W. S. 2007. Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death. Cancer Cell 12, 66-80.   DOI
25 Schuchmann, M., Schulze-Bergkamen, H., Fleischer, B., Schattenberg, J. M., Siebler, J., Weinmann, A., Teufel, A., Worns, M., Fischer, T., Strand, S., Lohse, A. W. and Galle, P. R. 2006. Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95- and TRAIL receptor-mediated apoptosis and chemotherapy. Oncol. Rep. 15, 227-230.
26 Shankar, S. and Srivastava, R. K. 2004. Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist. Updat. 7, 139-156.   DOI
27 Shetty, S., Graham, B. A., Brown, J. G., Hu, X., Vegh-Yarema, N., Harding, G., Paul, J. T. and Gibson, S. B. 2005. Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1. Mol. Cell Biol. 25, 5404-5416.   DOI
28 Singh, T. R., Shankar, S. and Srivastava, R. K. 2005. HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma. Oncogene 24, 4609-4623.   DOI
29 Sonnemann, J., Gange, J., Kumar, K. S., Muller, C., Bader, P. and Beck, J. F. 2005. Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines. Invest. New Drugs 23, 99-109.   DOI
30 Suliman, A., Lam, A., Datta, R and Srivastava, R. K. 2001. Intracellular mechanisms of TRAIL: apoptosis through mitochondrial- dependent and -independent pathways. Oncogene 20, 2122-2133.   DOI
31 Walczak, H., Miller, R. E., Ariail, K., Gliniak, B., Griffith, T. S., Kubin, M., Chin, W., Jones, J., Woodward, A., Le, T., Smith, C., Smolak, P., Goodwin, R. G., Rauch, C. T., Schuh, J. C. and Lynch, D. H. 1999. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat. Med. 5, 157-163.   DOI   ScienceOn
32 Wang, Y., Engels, I. H., Knee, D. A., Nasoff, M., Deveraux, Q. L. and Quon, K. C. 2004. Synthetic lethal targeting of MYC by activation of the DR5 death receptor pathway. Cancer Cell 5, 501-512.   DOI
33 Watanabe, K., Okamoto, K. and Yonehara, S. 2005. Sensitization of osteosarcoma cells to death receptor-mediated apoptosis by HDAC inhibitors through downregulation of cellular FLIP. Cell Death Differ. 12, 10-18.   DOI
34 Yuan, J., Minter-Dykhouse, K. and Lou, Z. 2009. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation. J. Cell Biol. 185, 203-211.   DOI
35 Zhang, L. and Fang, B. 2005. Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther. 12, 228-237.   DOI   ScienceOn