[논문]Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway

Chen, Liubo; Jiang, Kai; Chen, Haiyan; Tang, Yang; Zhou, Xinyi; Tan, Yinuo; Yuan, Ying; Xiao, Qian; Ding, Kefeng

doi:10.2147/CMAR.S169476

Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway 원문보기

Cancer management and research, v.11, 2019년, pp.95 - 105

Chen, Liubo (Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, dingkefeng@zju.edu.cn) , Jiang, Kai (qxiao3@zju.edu.cn) , Chen, Haiyan (Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, dingkefeng@zju.edu.cn) , Tang, Yang (qxiao3@zju.edu.cn) , Zhou, Xinyi (Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, dingkefeng@zju.edu.cn) , Tan, Yinuo (qxiao3@zj) , Yuan, Ying , Xiao, Qian , Ding, Kefeng

Abstract ▼ AI-Helper

ObjectivesDeguelin, a rotenoid extracted from Mundulea sericea (Leguminosae), exhibits antitumor effects on several types of human cancers. Due to the limited studies of deguelin on colorectal cancer (CRC), the present study was designed to investigate the antitumor effect of deguelin and to explore the underlying mechanism in CRC.Materials and methodsCell viability was assessed by the cell counting kit-8 (CCK-8) assay, and cell apoptosis was determined by the annexin v-propidium iodide staining using flow cytometry and Western blot in CRC cell lines after incubation with deguelin. The antitumor effect of deguelin was further evaluated in tumor xenograft models. Moreover, SB203580, a specific inhibitor of p38 MAPK, was used to confirm the involvement of p38 MAPK pathway in deguelin-induced apoptosis.ResultsDeguelin significantly inhibited cell proliferation and induced apoptosis in CRC cell lines (SW620 and RKO) in a time-dependent and dose-dependent manner. Western blot analysis also showed that the expression of proapoptotic proteins (cleaved caspase 3 and cleaved PARP) was upregulated, while that of antiapoptotic proteins (Bcl-2 and survivin) was downregulated after deguelin treatment in CRC cell lines. Moreover, oral administration of deguelin significantly suppressed tumor growth and induced apoptosis in subcutaneous xenograft mouse models without obvious toxicity. Additionally, Western blot revealed that deguelin-induced apoptosis might be regulated by the p38 MAPK pathway and inhibition of p38 MAPK could attenuate deguelin-induced proliferative inhibition and apoptosis in CRC cells.ConclusionCollectively, these results demonstrated that deguelin inhibited CRC cell growth by inducing apoptosis via activation of p38 MAPK pathway.

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참고문헌 (31)

1 Siegel RL Miller KD Jemal A Cancer statistics, 2016 CA Cancer J Clin 2016 66 1 7 30 26742998
2 Chen W Zheng R Baade PD Cancer statistics in China, 2015 CA Cancer J Clin 2016 66 2 115 132 26808342
3 Cersosimo RJ Management of advanced colorectal cancer, Part 1 Am J Health Syst Pharm 2013 70 5 395 406 23413162

상세보기
4 Murillo G Peng X Torres KE Mehta RG Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway Cancer Prev Res (Phila) 2009 2 11 942 950 19861542
5 Lee HY Oh SH Woo JK Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis J Natl Cancer Inst 2005 97 22 1695 1699 16288123

상세보기
6 Yan B Zhao D Yao Y Bao Z Lu G Zhou J Deguelin Induces the Apoptosis of Lung Squamous Cell Carcinoma Cells through Regulating the Expression of Galectin-1 Int J Biol Sci 2016 12 7 850 860 27313498

상세보기
7 Boreddy SR Srivastava SK Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model Oncogene 2013 32 34 3980 3991 22986522

상세보기
8 Lee HY Suh YA Kosmeder JW Pezzuto JM Hong WK Kurie JM Deguelin-induced inhibition of cyclooxygenase-2 expression in human bronchial epithelial cells Clin Cancer Res 2004 10 3 1074 1079 14871987

상세보기
9 Memmott RM Dennis PA The role of the Akt/mTOR pathway in tobacco carcinogen-induced lung tumorigenesis Clin Cancer Res 2010 16 1 4 10 20028747

상세보기
10 Oh SH Woo JK Jin Q Identification of novel antiangiogenic anticancer activities of deguelin targeting hypoxia-inducible factor-1 alpha Int J Cancer 2008 122 1 5 14 17764071

상세보기
11 Suh YA Kim JH Sung MA A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer Cancer Lett 2013 332 1 102 109 23348700

상세보기
12 Kang HW Kim JM Cha MY Jung HC Song IS Kim JS Deguelin, an Akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice Dig Dis Sci 2012 57 11 2873 2882 22623043
13 Jin Q Menter DG Mao L Hong WK Lee HY Survivin expression in normal human bronchial epithelial cells: an early and critical step in tumorigenesis induced by tobacco exposure Carcinogenesis 2008 29 8 1614 1622 18635526

상세보기
14 Loo DT In situ detection of apoptosis by the TUNEL assay: an overview of techniques Methods Mol Biol 2011 682 3 13 21057916

상세보기
15 Olson JM Hallahan AR p38 MAP kinase: a convergence point in cancer therapy Trends Mol Med 2004 10 3 125 129 15102355

상세보기
16 Cuadrado A Nebreda AR Mechanisms and functions of p38 MAPK signalling Biochem J 2010 429 3 403 417 20626350

상세보기
17 Xia Y Shen S Verma IM NF-κB, an active player in human cancers Cancer Immunol Res 2014 2 9 823 830 25187272
18 Hsu YC Chiang JH Yu CS Antitumor effects of deguelin on H460 human lung cancer cells in vitro and in vivo: Roles of apoptotic cell death and H460 tumor xenografts model Environ Toxicol 2017 32 1 84 98 26592500

상세보기
19 Mariani M Zannoni GF Sioletic S Gender influences the class III and V β-tubulin ability to predict poor outcome in colorectal cancer Clin Cancer Res 2012 18 10 2964 2975 22438565
20 Tamm I Wang Y Sausville E IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs Cancer Res 1998 58 23 5315 5320 9850056

상세보기
21 Cory S Adams JM The Bcl2 family: regulators of the cellular life-or-death switch Nat Rev Cancer 2002 2 9 647 656 12209154

상세보기
22 Adams JM Cory S The Bcl-2 apoptotic switch in cancer development and therapy Oncogene 2007 26 9 1324 1337 17322918

상세보기
23 Merino D Lok SW Visvader JE Lindeman GJ Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer Oncogene 2016 35 15 1877 1887 26257067

상세보기
24 Belmokhtar CA Hillion J Ségal-Bendirdjian E Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms Oncogene 2001 20 26 3354 3362 11423986

상세보기
25 Pozo-Guisado E Merino JM Mulero-Navarro S Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB Int J Cancer 2005 115 1 74 84 15688415
26 Grossi V Peserico A Tezil T Simone C p38α MAPK pathway: a key factor in colorectal cancer therapy and chemoresistance World J Gastroenterol 2014 20 29 9744 9758 25110412
27 Shin DY Lee WS Lu JN Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK Int J Oncol 2009 35 6 1499 504 19885574

상세보기
28 Pang H Cai L Yang Y Chen X Sui G Zhao C Knockdown of osteopontin chemosensitizes MDA-MB-231 cells to cyclophosphamide by enhancing apoptosis through activating p38 MAPK pathway Cancer Biother Radiopharm 2011 26 2 165 173 21539449

상세보기
29 Lou X Zhou Q Yin Y Zhou C Shen Y Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway Mol Cancer Ther 2009 8 5 1126 1136 19435873
30 Gan L Wang J Xu H Yang X Resistance to docetaxel-induced apoptosis in prostate cancer cells by p38/p53/p21 signaling Prostate 2011 71 11 1158 1166 21656826

상세보기
31 Pereira L Igea A Canovas B Dolado I Nebreda AR Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis mediated by reactive oxygen species and JNK EMBO Mol Med 2013 5 11 1759 1774 24115572

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Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway 원문보기

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