Author(s): Lin, SY (Lin, Shuw-Yuan); Lai, WW (Lai, Wan-Wen); Ho, CC (Ho, Chin-Chin); Yu, FS (Yu, Fu-Shun); Chen, GW (Chen, Guang-Wei); Yang, JS (Yang, Jai-Sing); Liu, KC (Liu, Kuo-Ching); Lin, ML (Lin, Meng-Liang); Wu, PP (Wu, Ping-Ping); Fan, MJ (Fan, Ming-Jen);
Chung, JG (Chung, Jing-Gung)
Title: Emodin Induces Apoptosis of Human Tongue Squamous Cancer SCC-4 Cells through Reactive Oxygen Species and Mitochondria-dependent Pathways
Source: ANTICANCER RESEARCH, 29 (1): 327-335 JAN 2009 Language: English
Document Type: Article
Author Keywords: ROS; ER stress; cell death; anthraquinone
KeyWords Plus: LEUKEMIA HL-60 CELLS; OXIDATIVE STRESS; DEATH; MECHANISMS;
ARREST; ANTHRAQUINONES; INVOLVEMENT; ACTIVATION; INDUCTION; ROOTS Abstract: Emodin was isolated from Rheum palmatum L. and exhibits an anticancer effect on human cancer cell lines, however, the molecular mechanisms of emodin-mediated apoptosis in human tongue cancer cells have not been fully investigated. In this study, treatment of human tongue cancer SCC-4 cells with various concentrations of emodin led to G(2)/M arrest through promoted p21 and Chk2 expression but inhibited cyclin B1 and cdc2; it also induced apoptosis through the pronounced release of cytochrome c from mitochondria and activations of caspase-9 and caspase-3. These events were accompanied by the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (Delta Psi(m)) and a decrease in the ratio of mitochondrial Bcl-2 and Box content; emodin also promoted the levels of GADD153 and GRP78. The free radical scavenger N-acetylcysteine and caspase inhibitors markedly blocked emodin-induced apoptosis. Taken together, these findings suggest that emodin mediated oxidative injury (DNA damage) based on ROS production and ER stress based on the levels of GADD153 and GRP78 that acts as an early and upstream change in the cell death cascade to caspase- and mitochondria-dependent signaling pathways, triggers mitochondrial dysfunction from Bcl-2 and Box modulation, mitochondrial cytochrome c release and caspase activation, consequently leading to apoptosis in SCC-4 cells.
Addresses: [Lin, Shuw-Yuan] HungKuang Univ, Dept Food & Nutr, Taichung, Taiwan; [Lai, Wan-Wen] China Med Univ, Dept Microbiol, Taichung 404, Taiwan; [Yu, Fu-Shun] China Med Univ, Dept Dent, Taichung 404, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan; [Wu, Ping-Ping] China Med Univ, Grad Inst Pharmaceut Chem, Sch Med Lab Sci, Taichung 404, Taiwan; [Liu, Kuo-Ching; Lin, Meng-Liang] China Med Univ, Sch Biotechnol, Taichung 404, Taiwan; [Wu, Ping-Ping] China Med Univ, Sch Pharm, Taichung 404, Taiwan; [Fan, Ming-Jen; Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Wufeng 413, Taichung County, Taiwan; [Chen, Guang-Wei] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Tradit Chinese Med, Kaohsiung, Taiwan; [Chung, Jing-Gung] China Med Univ, Dept Biol
Sci & Technol, Taichung 404, Taiwan
Reprint Address: Chung, JG, China Med Univ, Dept Biol Sci & Technol, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected]; [email protected] Funding Acknowledgement:
Funding Agency Grant Number
China Medical University CMU95-127
This work was supported by Grant CMU95-127 from China Medical University.
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Publisher: INT INST ANTICANCER RESEARCH
Publisher Address: EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE
ISSN: 0250-7005
29-char Source Abbrev.: ANTICANCER RES ISO Source Abbrev.: Anticancer Res.
Source Item Page Count: 9 Subject Category: Oncology ISI Document Delivery No.: 412NI
