Browse > Article
http://dx.doi.org/10.5352/JLS.2014.24.9.927

Sanguinarine Increases Sensitivity of Human Gastric Adenocarcinoma Cells to TRAIL-mediated Apoptosis by Inducing DR5 Expression and ROS Generation  

Lee, Taek Ju (Department of Internal Medicine, Dongeui University College of Korean Medicine)
Im, Yong Gyun (Department of Internal Medicine, Dongeui University College of Korean Medicine)
Choi, Woo Young (Division of Meridian and Structural Medicine, School of Korean Medicine, Busan National University)
Choi, Sung Hyun (Department of System Management, Korea Lift College)
Hwang, Won Deok (Department of Internal Medicine, Dongeui University College of Korean Medicine)
Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine, Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University)
Publication Information
Journal of Life Science / v.24, no.9, 2014 , pp. 927-934 More about this Journal
Abstract
Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAIL-mediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through upregulation of DR5 expression and ROS generation.
Keywords
Apoptosis; death receptor 5; reactive oxygen species; sanguinarine; TRAIL (tumor necrosis factor-related apoptosis-inducing ligand);
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Choi, W. Y., Jin, C. Y., Han, M. H., Kim, G. Y., Kim, N. D., Lee, W. H., Kim, S. K. and Choi, Y. H. 2009. Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. Anticancer Res 29, 4457-4465.
2 Ahmad, N., Gupta, S., Husain, M. M., Heiskanen, K. M. and Mukhtar, H. 2000. Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells. Clin Cancer Res 6, 1524-1528.
3 Bambagiotti-Alberti, M., Pinzauti, S., Moneti, G., Gratteri, P., Coran, S. A. and Vincieri, F. F. 1991. Characterization of Sanguinaria canadensis L. fluid extract by FAB mass spectrometry. J Pharm Biomed Anal 9, 1083-1087.   DOI   ScienceOn
4 Becci, P. J., Schwartz, H., Barnes, H. H. and Southard, G. L. 1987. Short-term toxicity studies of sanguinarine and of two alkaloid extracts of Sanguinaria canadensis L. J Toxicol Environ Health 20, 199-208.   DOI   ScienceOn
5 Bellail, A. C., Qi, L., Mulligan, P., Chhabra, V. and Hao, C. 2009. TRAIL agonists on clinical trials for cancer therapy:the promises and the challenges. Rev Recent Clin Trials 4, 34-41.   DOI   ScienceOn
6 Choi, Y. H., Choi, W. Y., Hong, S. H., Kim, S. O., Kim, G. Y., Lee, W. H. and Yoo, Y. H. 2009. Anti-invasive activity of sanguinarine through modulation of tight junctions and matrix metalloproteinase activities in MDA-MB-231 human breast carcinoma cells. Chem Biol Interact 179, 185-191.   DOI   ScienceOn
7 Choi, W. Y., Kim, G. Y., Lee, W. H. and Choi, Y. H. 2008. Sanguinarine, a benzophenanthridine alkaloid, induces apoptosis in MDA-MB-231 human breast carcinoma cells through a reactive oxygen species-mediated mitochondrial pathway. Chemotherapy 54, 279-287.   DOI   ScienceOn
8 Cretney, E., Takeda, K. and Smyth, M. J. 2007. Cancer: novel therapeutic strategies that exploit the TNF-related apoptosis- inducing ligand (TRAIL)/TRAIL receptor pathway. Int J Biochem Cell Biol 39, 280-286.   DOI   ScienceOn
9 Han, M. H., Yoo, Y. H. and Choi, Y. H. 2008. Sanguinarine-induced apoptosis in human leukemia U937 cells via Bcl-2 downregulation and caspase-3 activation. Chemotherapy 54, 157-165.   DOI   ScienceOn
10 Fulda, S. 2008. Modulation of TRAIL-induced apoptosis by HDAC inhibitors. Curr Cancer Drug Targets 8, 132-140.   DOI   ScienceOn
11 Galluzzi, L., Larochette, N., Zamzami, N. and Kroemer, G. 2006. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25, 4812-4830.   DOI   ScienceOn
12 Han, M. H., Kim, S. O., Kim, G. Y., Kwon, T. K., Choi, B. T., Lee, W. H. and Choi, Y. H. 2007. Induction of apoptosis by sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt. Anticancer Drugs 18, 913-921.
13 Han, M. H., Kim, G. Y., Yoo, Y. H. and Choi, Y. H. 2013. Sanguinarine induces apoptosis in human colorectal cancer HCT-116 cells through ROS-mediated Egr-1 activation and mitochondrial dysfunction. Toxicol Lett 220, 157-166.   DOI   ScienceOn
14 Han, M. H., Park, C., Jin, C. Y., Kim, G. Y., Chang, Y. C., Moon, S. K., Kim, W. J. and Choi, Y. H. 2013. Apoptosis induction of human bladder cancer cells by sanguinarine through reactive oxygen species-mediated up-regulation of early growth response gene-1. PLoS One 8, e63425.   DOI
15 Henson, E. S., Johnston, J. B. and Gibson, S. B. 2008. The role of TRAIL death receptors in the treatment of hematological malignancies. Leuk Lymphoma 49, 27-35.
16 Jin, C. Y., Park, C., Cheong, J., Choi, B. T., Lee, T. H., Lee, J. D., Lee, W. H., Kim, G. Y., Ryu, C. H. and Choi, Y. H. 2007. Genistein sensitizes TRAIL-resistant human gastric adenocarcinoma AGS cells through activation of caspase-3. Cancer Lett 257, 56-64.   DOI   ScienceOn
17 Hussain, A. R., Al-Jomah, N. A., Siraj, A. K., Manogaran, P., Al-Hussein, K., Abubaker, J., Platanias, L. C., Al-Kuraya, K. S. and Uddin, S. 2007. Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells. Cancer Res 67, 3888-3897.   DOI   ScienceOn
18 Jeong, S. Y. and Seol, D. W. 2008. The role of mitochondria in apoptosis. BMB Rep 41, 11-22.   과학기술학회마을   DOI
19 Kim, S., Lee, T. J., Leem, J., Choi, K. S., Park, J. W. and Kwon, T. K. 2008. Sanguinarine-induced apoptosis: Generation of ROS, down-regulation of BCL-2, c-FLIP, and synergy with TRAIL. J Cell Biochem 104, 895-907.   DOI   ScienceOn
20 Kemeny-Beke, A., Aradi, J., Damjanovich, J., Beck, Z., Facsko, A., Berta, A. and Bodnar, A. 2006. Apoptotic response of uveal melanoma cells upon treatment with chelidonine, sanguinarine and chelerythrine. Cancer Lett 237, 67-75.   DOI   ScienceOn
21 Kroemer, G., Galluzzi, L. and Brenner, C. 2007. Mitochondrial membrane permeabilization in cell death. Physiol Rev 87, 99-163.   DOI   ScienceOn
22 Lenfeld, J., Kroutil, M., Marsalek, E., Slavik, J., Preininger, V. and Simanek, V. 1981. Antiinflammatory activity of quaternary benzophenanthridine alkaloids from Chelidonium majus. Planta Med 43, 161-165.   DOI   ScienceOn
23 Matkar, S. S., Wrischnik, L. A. and Hellmann-Blumberg, U. 2008. Sanguinarine causes DNA damage and p53-independent cell death in human colon cancer cell lines. Chem Biol Interact 172, 63-71.   DOI   ScienceOn
24 Seifen, E., Adams, R. J. and Riemer, R. K. 1979. Sanguinarine: a positive inotropic alkaloid which inhibits cardiac $Na^+$, $K^+$-ATPase. Eur J Pharmacol 60, 373-377.   DOI   ScienceOn
25 Merino, D., Lalaoui, N., Morizot, A., Solary, E. and Micheau, O. 2007. TRAIL in cancer therapy: present and future challenges. Expert Opin Ther Targets 11, 1299-1314.   DOI   ScienceOn
26 Yang, L. Q., Fang, D. C., Wang, R. Q. and Yang, S. M. 2004. Effect of NF-kB, survivin, BCL-2 and caspase-3 on apoptosis of gastric cancer cells induced by tumor necrosis factor-related apoptosis inducing ligand. World J Gastroenterol 10, 22-25.   DOI
27 Mitscher, L. A., Park, Y. H., Clark, D., Clark III, G. W., Hammesfahr, P. D., Wu, W. N. and Beal, J. L. 1978. Antimicrobial agents from higher plants. An investigation of Hunnemannia fumariaefolia pseudoalcoholates of sanguinarine and chelerythrine. Lloydia 41, 145-150.
28 Wu, X. X., Ogawa, O. and Kakehi, Y. 2004. TRAIL and chemotherapeutic drugs in cancer therapy. Vitam Horm 67, 365-383.   DOI   ScienceOn
29 Zhang, L. and Fang, B. 2005. Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 12, 228-237.   DOI   ScienceOn
30 Zhou, P., Cheng, S. W., Yang, R., Wang, B. and Liu, J. 2012. Combination chemoprevention: future direction of colorectal cancer prevention. Eur J Cancer Prev 21, 231-240.   DOI
31 Jin, C. Y., Moon, D. O., Lee, J. D., Heo, M. S., Choi, Y. H., Lee, C. M., Park, Y. M. and Kim, G. Y. 2007. Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis through downregulation of ERK and AKT in lung adenocarcinoma A549 cells. Carcinogenesis 28, 1058-1066.