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Vol. 65 No. 6: Issue 6

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Sesamolin exerts anti-proliferative and apoptotic effect on human colorectal cancer cells via inhibition of JAK2/STAT3 signaling pathway

https://doi.org/10.14715/cmb/2019.65.6.16
Di Wu
Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China
Xin-Ping Wang
Department of General Surgery, GuangRen Hospital of Xi'an Jiaotong University, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, China
Wei Zhang
Department of General Surgery, GuangRen Hospital of Xi'an Jiaotong University, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, China

Corresponding Author(s) : Wei Zhang

vcnvr0@163.com

Cellular and Molecular Biology, Vol. 65 No. 6: Issue 6

Abstract

Colorectal cancer (CRC) is a common malignant tumor that seriously threatens human health and quality of life. At present, the search for safe and more effective treatment for CRC has become necessary. The present study investigated the anti-proliferative and apoptotic effects of sesamolin on human colorectal cancer (HCT116) cells, and the underlying mechanism. Cell proliferation was determined using MTT assay, while the expressions of JAK2, STAT3 and p-STA3 were determined using Western blotting. The levels of expression of matrix metalloproteinases-1, 2 and 9 (MMP1, MMP2 and MMP9) were determined using real-time quantitative polymerase chain reaction (qRT-PCR). The degree of migration and invasion of the cells was assessed using wound healing assay. The results of MTT assay showed that sesamolin significantly and time- and dose-dependently inhibited the proliferation of HCT116 cells (p < 0.05). Treatment of HCT116 cells with sesamolin significantly inhibited their migratory ability (p < 0.05). The expressions of p-JAK2 and p-STAT3 were significantly down-regulated 48 h after 20 µM of JAK2 specific inhibitor (AG490) was added to HCT116 cells (p < 0.05). The expression of p-STAT3 was also significantly and dose-dependently down-regulated 6 h after treatment of HCT116 cells with sesamolin (p < 0.05). Sesamolin and AG490 had synergistic effect and their combination significantly down-regulated the expression of p-STAT3, when compared with sesamolin alone (p < 0.05). Treatment of HCT116 cells with sesamolin significantly and dose-dependently reduced the levels of IL-6-induced expressions of MMP-1, MMP-2 and MMP-9 (p < 0.05). These results suggest that sesamolin induces apoptosis in HCT116 cells and prevents cell invasion via inhibition of the JAK2/STAT3 signaling pathway.

Keywords

Colorectal cancer Sesamolin JAK2/STAT3 pathway Metastasis Expression.
Wu, D., Wang, X.-P., & Zhang, W. (2019). Sesamolin exerts anti-proliferative and apoptotic effect on human colorectal cancer cells via inhibition of JAK2/STAT3 signaling pathway. Cellular and Molecular Biology, 65(6), 96–100. https://doi.org/10.14715/cmb/2019.65.6.16
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References
  1. Li S, Tian J, Zhang H, Zhou S, Wang X, Zhang L, et al. Down-regulating IL-6/GP130 targets improved the anti-tumor effects of 5-fluorouracil in colon cancer. APOPTOSIS 2018; 23: 356-374.
  2. Corvinus FM, Orth C, Moriggl R, Tsareva SA, Wagner S, Pfitzner EB, et al. Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia 2005; 7: 545-555.
  3. Helling TS, Martin MJ. Cause of death from liver metastases in colorectal cancer. Ann Surg Oncol 2014; 21: 501-506.
  4. Kim JH, Lee SC, Ro J, Kang HS, Kim HS, Yoon SJ. Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines. Biochem Pharmacol 2010; 79 (3): 373-380.
  5. Han S, Jeong AJ, Yang H, Kang KB, Lee H, Yi EH, et al. Ginsenoside 20 (S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells. J Ethnopharmacol 2016; 194: 83-90.
  6. Jeng K, Hou RJ. Sesamin and sesamolin: nature's therapeutic lignans. Current Enzyme Inhibition 2005; 1: 11-20.
  7. Jeon JS, Park CL, Syed AS, Kim YM, Cho IJ, Kim CY. Preparative separation of sesamin and sesamolin from defatted sesame meal via centrifugal partition chromatography with consecutive sample injection. J Chromatogr B Analyt Technol Biomed Life Sci 2016; 1011: 108-113.
  8. Dar AA, Verma NK, Arumugam NJ. Products: An updated method for isolation, purification and characterization of clinically important antioxidant lignans–Sesamin and sesamolin, from sesame oil. Industrial Crops and Products 2015; 64: 201-208.
  9. Kim JH, Lee JK. Sesamolin enhances NK cell lysis activity by increasing the expression of NKG2D ligands on Burkitt's lymphoma cells. Int Immunopharmacol 2015; 28: 977-984.
  10. Plumb JA. Cell sensitivity assays : the MTT assay. Methods Mol Med 2011; 88: 237-245.
  11. Gupta SC, Kim JH, Prasad S, Aggarwal BB. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 2010; 29: 405-434.
  12. Zou J, Mi L, Yu XF, Dong JJ. Interaction of 14-3-3σ with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells. World J Gastroenterol 2013; 19: 3770.
  13. Wang ZX, Cao JX, Liu ZP, Cui YX, Li CY, Li D, et al. Combination of chemotherapy and immunotherapy for colon cancer in China: a meta-analysis. World J Gastroenterol 2014; 20: 1095.
  14. Kamal-Eldin A, Moazzami A, Washi SJ. Nutrition, agriculture: Sesame seed lignans: potent physiological modulators and possible ingredients in functional foods & nutraceuticals. Recent Pat Food Nutr Agric 2011; 3: 17-29.
  15. Ide T, Lim JS, Odbayar TO, Nakashima YJ. Comparative study of sesame lignans (sesamin, episesamin and sesamolin) affecting gene expression profile and fatty acid oxidation in rat liver. J Nutr Sci Vitaminol (Tokyo) 2009; 55: 31-43.
  16. Yu H, Pardoll D, Jove RJ. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009; 9: 798.
  17. Turkson J, Jove R. STAT proteins: novel molecular targets for cancer drug discovery. Oncogene 2000; 19: 6613.
  18. Devarajan E, Huang S. STAT3 as a central regulator of tumor metastases. Curr Mol Med 2009; 9: 626-633.
  19. Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L, et al. Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol 2002; 102: 169-178.
  20. Chiba T, Yamada M, Aiso S. Targeting the JAK2/STAT3 axis in Alzheimer's disease. Expert Opin Ther Targets 2009; 13: 1155-1167.
  21. Xu J, Zhang C, Tang B, Hao Y, Chen J, Liu T, et al. Effect of JAK2/STAT3/vimentin signaling pathway on proliferation and migration of human colon cancer cells. Zhonghua Wei Chang Wai Ke Za Zhi 2010; 13: 282-285.
  22. Gurbuz V, Konac E, Varol N, Yilmaz A, Gurocak S, Menevse S, et al. Effects of AG490 and S3I"‘201 on regulation of the JAK/STAT3 signaling pathway in relation to angiogenesis in TRAIL"‘resistant prostate cancer cells in vitro. Oncol Lett 2014; 7: 755-763.
  23. Germain D, Frank DA. Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin Cancer Res 2007; 13: 5665-5669.
  24. Shih WL, Yu FL, Chang CD, Liao MH, Wu HY, Lin PY. Suppression of AMF/PGI"mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model. Mol Carcinog 2013; 52: 800-812.
  25. Madsen CD, Hooper S, Tozluoglu M, Bruckbauer A, Fletcher G, Erler JT, et al. STRIPAK components determine mode of cancer cell migration and metastasis. Nat Cell Biol 2015; 17: 68.
  26. Tabouret E, Bertucci F, Pierga JY, Petit T, Levy C, Ferrero JM, et al. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study. Oncotarget 2016; 7: 18531.
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