Author(s): Hsia, TC (Hsia, Te-Chun); Yang, JS (Yang, Jai-Sing); Chen, GW (Chen, Guang- Wei); Chiu, TH (Chiu, Tsan-Hung); Lu, HF (Lu, Hsu-Feng); Yang, MD (Yang, Mei-Due); Yu, FS (Yu, Fu-Shun); Liu, KC (Liu, Kuo-Ching); La, KC (La, Kuang-Chi); Lin, CC (Lin, Chin- Chung); Chung, JG (Chung, Jing-Gung)
Title: The Roles of Endoplasmic Reticulum Stress and Ca2+ on Rhein-induced apoptosis in A- 549 Human Lung Cancer cells
Source: ANTICANCER RESEARCH, 29 (1): 309-318 JAN 2009 Language: English
Document Type: Article
Author Keywords: Rhein; apoptosis; caspase-3; ROS; mitochondria membrane potential;
cytochrome c
KeyWords Plus: LEUKEMIA-CELLS; ALOE-EMODIN; HL-60 CELLS; IN-VITRO; DEATH;
MITOCHONDRIA; CYTOTOXICITY; CARCINOMA; TUMOR; INVOLVEMENT
Abstract: Although rhein has been shown to induce apoptosis in several cancer cell lines, the mechanism of action of rhein-induced cell cycle arrest and apoptosis at the molecular level is not well known. In this study, the mechanism of rhein action on A-549 human lung cancer cells was investigated. Rhein induced G(0)/G(1) arrest through inhibition of cyclin D3, Cdk4 and Cdk6. The efficacious induction of apoptosis was observed at 50 mu M for 12 h and up to 72 h as examined by a flow cytometric method. Flow cytometric analysis demonstrated that rhein increased the levels of GADD153 and GRP78, both hallmarks of endoplasmic reticulum stress, promoted ROS and Ca2+ production, induced the loss of mitochondrial membrane potential (Delta Psi(m)), promoted cytochrome c release from mitochondria, promoted capase- 3 activation and led to apoptosis. Rhein also increased the levels of p53, p21 and Bax but reduced the level of Bcl-2. The Ca2+ chelator BAPTA was added to the cells before rhein treatment, thus blocking the Ca2+ production and inhibiting rhein-induced apoptosis in A-549 cells. Our data demonstrate that rhein induces apoptosis in A-549 cells via a Ca2+-dependent mitochondrial pathway.
Addresses: [Hsia, Te-Chun] China Med Univ, Dept Internal Med, Taichung 404, Taiwan;
[Chiu, Tsan-Hung] China Med Univ, Dept OBS GYN, Taichung 404, Taiwan; [Yang, Mei-Due]
China Med Univ, Dept Surg, Taichung 404, Taiwan; [La, Kuang-Chi] China Med Univ, Dept Med, Taichung 404, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan; [Liu, Kuo-Ching] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung 404, Taiwan; [Yu, Fu-Shun] China Med Univ, Sch Dent, Taichung 404, Taiwan; [Chen, Guang- Wei] Kaohsiung Med Univ, Dept Tradit Chinese Med, Chung Ho Mem Hosp, Kaohsiung, Taiwan; [Lin, Chin-Chung] Fong Yuan Hosp, Fong Yuan, Taiwan; [Lu, Hsu-Feng] Cheng Hsin Rehabil Med Ctr, Dept Clin Pathol, Taipei, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Taichung, Taichung County, 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: jgchung@mail.cmu.edu.tw Funding Acknowledgement:
Funding Agency Grant Number
National Science Council of Taiwan NSC-93-2745-B-039-003-URD NSC-94-2745-B-039-002-URD
This work was supported by grants NSC-93-2745-B-039-003-URD and NSC-94-2745-B-039- 002-URD from the National Science Council of Taiwan.
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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: 10 Subject Category: Oncology ISI Document Delivery No.: 412NI
