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Rhein Induced Apoptosis through the Endoplasmic Reticulum Stress, Caspase- and Mitochondria-dependent Pathways in SCC-4 Human Tongue Squamous Cancer Cells

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Author(s): Lai, WW (Lai, Wan-Wen); Yang, JS (Yang, Jai-Sing); Lai, KC (Lai, Kuang-Chi);

Kuo, CL (Kuo, Chao-Lin); Hsu, CK (Hsu, Cheng-Kuang); Wang, CK (Wang, Chien-Kuo);

Chang, CY (Chang, Ching-Yao); Lin, JJ (Lin, Jen-Jyh); Tang, NY (Tang, Nou-Ying); Chen, PY (Chen, Po-Yuan); Huang, WW (Huang, Wen-Wen); Chung, JG (Chung, Jing-Gung)

Title: Rhein Induced Apoptosis through the Endoplasmic Reticulum Stress, Caspase- and Mitochondria-dependent Pathways in SCC-4 Human Tongue Squamous Cancer Cells Source: IN VIVO, 23 (2): 309-316 MAR-APR 2009

Language: English Document Type: Article

Author Keywords: Rhein; apoptosis; caspase; mitochondria; DNA damage; SCC-4 human tongue cancer cells

KeyWords Plus: ACTIVATION; PROTEOLYSIS; PROTEASES

Abstract: Rhein, an anthraquinone compound, can be found in the rhizome of rhubarb, a traditional Chinese medicine herb showing antitumor activity. In this study, it was observed that rhein induced S-phase arrest through the inhibition of p53, cyclin A and E and it induced apoptosis through the endoplasmic reticulum stress by the production of reactive oxygen species (ROS) and Ca2+ release, mitochondrial dysfunction, and caspase-8, -9 and -3 activation in human tongue cancer cell line (SCC-4). The most efficient induction of apoptosis was observed at 30 mu M for 24 h. Mechanistic analysis demonstrated that rhein induced changes in the ratio of Bax/Bcl-2 based on the decrease of Bcl-2 levels, the loss of mitochondrial membrane potential, cytochrome c release from the mitochondria and the activation of caspase-9 and -3. The data demonstrated that rhein induces apoptosis in SCC-4 cells via caspase, ROS and mitochondrial death pathways.

Addresses: [Lai, Wan-Wen; Chen, Po-Yuan; Huang, Wen-Wen; Chung, Jing-Gung] China Med Univ, Dept Biol Sci & Technol, Taichung 40402, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 40402, Taiwan; [Kuo, Chao-Lin] China Med Univ, Inst Chinese Pharmaceut Sci, Taichung 40402, Taiwan; [Tang, Nou-Ying] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan; [Lai, Kuang-Chi] China Med Univ, Sch Med, Dept Med, Taichung 40402, Taiwan; [Lai, Kuang-Chi] China Med Univ, Beigang Hosp, Dept Surg, Taichung 40402, Yunlin County, Taiwan; [Hsu, Cheng-Kuang] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan; [Wang, Chien-Kuo; Chang, Ching-Yao] Asia Univ, Dept

Biotechnol, Taichung, Taiwan; [Lai, Kuang-Chi] China Med Univ Hosp, Dept Med, Div Cardiol, Taichung, Taiwan

Reprint Address: Chung, JG, China Med Univ, Dept Biol Sci & Technol, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.

E-mail Address: [email protected] Funding Acknowledgement:

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China Medical University, Taichung, Taiwan, R.O.C. CMU96-087

This work was Supported by Grant CMU96-087 from China Medical University, Taichung, Taiwan, R.O.C.

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Cited Reference Count: 26 Times Cited: 2

Publisher: INT INST ANTICANCER RESEARCH

Publisher Address: EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE

ISSN: 0258-851X

29-char Source Abbrev.: IN VIVO

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ISO Source Abbrev.: In Vivo Source Item Page Count: 8

Subject Category: Medicine, Research & Experimental ISI Document Delivery No.: 430ZA

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