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http://dx.doi.org/10.7314/APJCP.2014.15.13.5201

Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway  

Xie, Mei-Juan (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Ma, Yi-Hua (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Miao, Lin (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Wang, Yan (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Wang, Hai-Zhen (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Xing, Ying-Ying (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Xi, Tao (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Lu, Yuan-Yuan (State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.13, 2014 , pp. 5201-5205 More about this Journal
Abstract
Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.
Keywords
Emodin; Human colon cancer HCT116 cells; ROS; p53; Mitochondrial apoptosis;
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1 Antonsson B, Conti F, Ciavatta A, et al (1997). Inhibition of Bax channel-forming activity by Bcl-2. Science, 277, 370-2.   DOI   ScienceOn
2 Subramaniam A, Shanmugam MK, Ong TH, et al (2013). Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3. Br J Pharmacol, 170, 807-21.   DOI   ScienceOn
3 Toshiyuki M and Reed JC (1995). Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell, 80, 293-9.   DOI   ScienceOn
4 Tsujimoto Y, Shimizu S (2000). Bcl-2 family: life-or-death switch. FEBS Lett, 466, 6-10.   DOI   ScienceOn
5 Zhou Y, Hileman EO, Plunkett W, et al (2003). Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. Blood, 101, 4098-104.   DOI   ScienceOn
6 Manu KA, Shanmugam MK, Ong TH, et al (2013). Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS One, 8, 57015.   DOI
7 Lin SY, Lai WW, Ho CC, et al (2009). Emodin induces apoptosis of human tongue squamous cancer SCC-4 Cells through reactive oxygen species and mitochondria-dependent pathways. Anticancer Res, 29, 327-35.
8 Lu YY, Zhang JL, Qian JM (2008). The effect of emodin on VEGF receptors in human colon cancer cells. Cancer Biother Radio, 23, 222-8.   DOI   ScienceOn
9 Ma YS, Weng SW, Lin MW, et al (2012). Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: Roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol, 50, 1271-8.   DOI   ScienceOn
10 Murphy RC, Schneider E, Kinnally KW (2001). Overexpression of Bcl-2 suppresses the calcium activation of a mitochondrial megachannel. FEBS Lett, 497, 73-6.   DOI   ScienceOn
11 Pelicano H, Carney D, Huang P (2004). ROS stress in cancer cells and therapeutic implications. Drug Resist Updat, 7, 97-110.   DOI   ScienceOn
12 Petit PX, Susin SA, Zamzami N, et al (1996). Mitochondria and programmed cell death: back to the future. FEBS Lett, 396, 7-13.   DOI   ScienceOn
13 Rengarajan T, Nandakumar N, Rajendran P, et al (2014). D-Pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-kappa B. Asian Pac J Cancer Prev, 15, 1757-62.   DOI   ScienceOn
14 Su Y-T, Chang H-L, Shyue S-K, Hsu S-L (2005). Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem Pharmacol, 70, 229-41.   DOI   ScienceOn
15 International Agency for Research on Cancer (2014a). Cancer Fact Sheets. in Globocan2012 Estimated Incidence, Mortality and Prevalence Worldwide in 2012, DOI: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
16 He L, Bi J-J, Guo Q, et al (2012). Effects of emodin extracted from Chinese herbs on proliferation of non-small cell lung cancer and underlying mechanisms. Asian Pac J Cancer Prev, 13, 1505-10.   과학기술학회마을   DOI   ScienceOn
17 Lai JM, Chang JT, Wen CL, Hsu SL (2009). Emodin induces a reactive oxygen species-dependent and ATM-p53-Bax mediated cytotoxicity in lung cancer cells. Eur J Pharmacol, 623, 1-9.   DOI   ScienceOn
18 Huang J, Yang J, Maity B, et al (2011). Regulator of G protein signaling 6 mediates doxorubicin-induced ATM and p53 activation by a reactive oxygen species.dependent mechanism. Cancer Res, 71, 6310-9.   DOI
19 International Agency for Research on Cancer (2014b). population Fact Sheets. in Globocan2012 Estimated Incidence, Mortality and Prevalence Worldwide in 2012, DOI: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
20 Kinnally KW, Antonsson B (2007). A tale of two mitochondrial channels, MAC and PTP, in apoptosis. Apoptosis, 12, 857-68.   DOI
21 Lin JG, Chen GW, Li TM, et al (2006). Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53 dependent apoptotic pathway. J Urol, 175, 343-7.   DOI   ScienceOn
22 Lin S-Z, Wei W-T, Chen H, et al (2012). Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis. PloS One, 7, 42146.   DOI
23 Green DR, Reed JC (1998). Mitochondria and apoptosis. Science, 281, 1309-12.   DOI   ScienceOn
24 Chipuk JE, Kuwana T, Bouchier-Hayes L, et al (2004). Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 303, 1010-4.   DOI   ScienceOn
25 China Pharmacopoeia Committee (2010). Traditional Chinese Patent Medicines and Simple Preparations. in Pharmacopoeia of the People's Republic of China, Eds C. P. Committee. China Chemical Industry Press. Beijing.
26 Huang FJ, Hsuuw YD, Chan WH (2013). Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells. Int J Mol Sci, 14, 20139-56.   DOI
27 Guo Z, Kozlov S, Lavin MF, et al (2010). ATM activation by oxidative stress. Science, 330, 517-21.   DOI   ScienceOn
28 Hassan ZK, Elamin MH, Omer SA, et al (2013). Oleuropein induces apoptosis via the p53 pathway in breast cancer cells. Asian Pac J Cancer Prev, 14, 6739-42.   과학기술학회마을   DOI   ScienceOn
29 Dejean LM, Martinez-Caballero S, Guo L, et al (2005). Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Mol Biol Cell, 16, 2424-32.   DOI   ScienceOn
30 Yin R, Bao W, Xing Y, et al (2012). MiR-19b-1 inhibits angiogenesis by blocking cell cycle progression of endothelial cells. Biochem Biophys Res Commun, 417, 771-6.   DOI   ScienceOn