caa a22 4500 445853417 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00204-011-0670-9 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0670-9 Effect of diindolylmethane on Ca2+ movement and viability in HA59T human hepatoma cells [Elektronische Daten] [Jin-Shiung Cheng, Su-Shung Shu, Chun-Chi Kuo, Chiang-Ting Chou, Wei-Lun Tsai, Yi-Chien Fang, Li-Ni Kuo, Jeng-Hsien Yeh, Wei-Chuan Chen, Jau-Min Chien, Ti Lu, Chih-Chuan Pan, He-Hsiung Cheng, Kuo-Liang Chai, Chung-Ren Jan] 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 1-50μM 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 10-75μM, 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 (25-50μM) 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. Springer-Verlag, 2011 Ca2+ nationallicence Diindolylmethane nationallicence HA59T nationallicence Hepatoma nationallicence Cheng Jin-Shiung Department of Medicine, Yongkang Veterans Hospital, 710, Tainan, Taiwan aut Shu Su-Shung Department of Surgery, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Kuo Chun-Chi Department of Nursing, Tzu Hui Institute of Technology, 926, Pingtung, Taiwan aut Chou Chiang-Ting Institute of Nursing and Department of Nursing, Chang Gung Institute of Technology, Chiayi Campus, 613, Chiayi, Taiwan aut Tsai Wei-Lun Department of Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Fang Yi-Chien Laboratory Medicine Division, Zuoying Armed Forces General Hospital, 813, Kaohsiung, Taiwan aut Kuo Li-Ni Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Yeh Jeng-Hsien Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Chen Wei-Chuan Department of Surgery, Ping Tung Christian Hospital, 900, Ping Tung, Taiwan aut Chien Jau-Min Department of Pediatrics, Ping Tung Christian Hospital, 900, Ping Tung, Taiwan aut Lu Ti Department of Psychiatry, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Pan Chih-Chuan Department of Psychiatry, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Cheng He-Hsiung Chang Bing Show Chwan Memorial Hospital, 505, Changhua County, Taiwan aut Chai Kuo-Liang Department of Medicine, Yongkang Veterans Hospital, 710, Tainan, Taiwan aut Jan Chung-Ren Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1257-1266 0340-5761 85:10<1257 2011 85 204 https://doi.org/10.1007/s00204-011-0670-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0670-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cheng Jin-Shiung Department of Medicine, Yongkang Veterans Hospital, 710, Tainan, Taiwan aut NATIONALLICENCE 700 1- Shu Su-Shung Department of Surgery, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Kuo Chun-Chi Department of Nursing, Tzu Hui Institute of Technology, 926, Pingtung, Taiwan aut NATIONALLICENCE 700 1- Chou Chiang-Ting Institute of Nursing and Department of Nursing, Chang Gung Institute of Technology, Chiayi Campus, 613, Chiayi, Taiwan aut NATIONALLICENCE 700 1- Tsai Wei-Lun Department of Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Fang Yi-Chien Laboratory Medicine Division, Zuoying Armed Forces General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Kuo Li-Ni Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Yeh Jeng-Hsien Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Chen Wei-Chuan Department of Surgery, Ping Tung Christian Hospital, 900, Ping Tung, Taiwan aut NATIONALLICENCE 700 1- Chien Jau-Min Department of Pediatrics, Ping Tung Christian Hospital, 900, Ping Tung, Taiwan aut NATIONALLICENCE 700 1- Lu Ti Department of Psychiatry, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Pan Chih-Chuan Department of Psychiatry, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Cheng He-Hsiung Chang Bing Show Chwan Memorial Hospital, 505, Changhua County, Taiwan aut NATIONALLICENCE 700 1- Chai Kuo-Liang Department of Medicine, Yongkang Veterans Hospital, 710, Tainan, Taiwan aut NATIONALLICENCE 700 1- Jan Chung-Ren Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1257-1266 0340-5761 85:10<1257 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer