Effect of diindolylmethane on Ca2+ movement and viability in HA59T human hepatoma cells
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  • 作者:Jin-Shiung Cheng (1)
    Su-Shung Shu (2)
    Chun-Chi Kuo (3)
    Chiang-Ting Chou (4)
    Wei-Lun Tsai (5)
    Yi-Chien Fang (6)
    Li-Ni Kuo (7)
    Jeng-Hsien Yeh (7)
    Wei-Chuan Chen (8)
    Jau-Min Chien (9)
    Ti Lu (10)
    Chih-Chuan Pan (10)
    He-Hsiung Cheng (11)
    Kuo-Liang Chai (1)
    Chung-Ren Jan (12)
  • 关键词:Ca2+ ; Diindolylmethane ; HA59T ; Hepatoma
  • 刊名:Archives of Toxicology
  • 出版年:2011
  • 出版时间:October 2011
  • 年:2011
  • 卷:85
  • 期:10
  • 页码:1257-1266
  • 全文大小:1872KB
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  • 作者单位:Jin-Shiung Cheng (1)
    Su-Shung Shu (2)
    Chun-Chi Kuo (3)
    Chiang-Ting Chou (4)
    Wei-Lun Tsai (5)
    Yi-Chien Fang (6)
    Li-Ni Kuo (7)
    Jeng-Hsien Yeh (7)
    Wei-Chuan Chen (8)
    Jau-Min Chien (9)
    Ti Lu (10)
    Chih-Chuan Pan (10)
    He-Hsiung Cheng (11)
    Kuo-Liang Chai (1)
    Chung-Ren Jan (12)

    1. Department of Medicine, Yongkang Veterans Hospital, Tainan, 710, Taiwan
    2. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
    3. Department of Nursing, Tzu Hui Institute of Technology, Pingtung, 926, Taiwan
    4. Institute of Nursing and Department of Nursing, Chang Gung Institute of Technology, Chiayi Campus, Chiayi, 613, Taiwan
    5. Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
    6. Laboratory Medicine Division, Zuoying Armed Forces General Hospital, Kaohsiung, 813, Taiwan
    7. Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
    8. Department of Surgery, Ping Tung Christian Hospital, Ping Tung, 900, Taiwan
    9. Department of Pediatrics, Ping Tung Christian Hospital, Ping Tung, 900, Taiwan
    10. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
    11. Chang Bing Show Chwan Memorial Hospital, Changhua County, 505, Taiwan
    12. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
  • ISSN:1432-0738
文摘
The effect of diindolylmethane, a natural compound derived from indole-3-carbinol in cruciferous vegetables, on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in HA59T human hepatoma cells is unclear. This study explored whether diindolylmethane changed [Ca2+]i in HA59T cells. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Diindolylmethane at concentrations of 1-0?μM evoked a [Ca2+]i rise in a concentration-dependent manner. The signal was reduced by removing Ca2+. Diindolylmethane-induced Ca2+ influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators but was inhibited by aristolochic acid. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca2+]i rise. Incubation with diindolylmethane inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca2+]i rise. At concentrations of 10-5?μM, diindolylmethane killed cells in a concentration-dependent manner. The cytotoxic effect of diindolylmethane was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N-N-tetraacetic acid. Propidium iodide staining data suggest that diindolylmethane (25-0?μM) induced apoptosis in a concentration-dependent manner. Collectively, in HA59T cells, diindolylmethane induced a [Ca2+]i rise by causing phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive channels. Diindolylmethane induced cell death that may involve apoptosis.

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