The Mechanism of Safrole-Induced [Ca2+]i Rises and Non-Ca2+-Triggered Cell Death in SCM1 Human Gastric Cancer Cells

被引:2
作者
Hung, Tzu-Yi [1 ]
Chou, Chiang-Ting [2 ,3 ]
Sun, Te-Kung [4 ]
Liang, Wei-Zhe [5 ]
Cheng, Jin-Shiung [6 ]
Fang, Yi-Chien [1 ]
Li, Yih-Do [1 ]
Shieh, Pochuen [7 ]
Ho, Chin-Man [5 ]
Kuo, Chun-Chi [8 ]
Lin, Jia-Rong [5 ]
Kuo, Daih-Huang [7 ]
Jan, Chung-Ren [5 ]
机构
[1] Kaohsiung Armed Forces Gen Hosp, Dept Lab Med, Zuoying Branch, Kaohsiung 81345, Taiwan
[2] Chang Gung Univ Sci & Technol, Div Basic Med Sci, Dept Nursing, Chiayi 61363, Taiwan
[3] Chang Gung Univ Sci & Technol, Chron Dis & Hlth Promot Res Ctr, Chiayi 61363, Taiwan
[4] St Joseph Hosp, Dept Pediat, Kaohsiung 80288, Taiwan
[5] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung 81362, Taiwan
[6] Kaohsiung Vet Gen Hosp, Dept Med, Kaohsiung 81362, Taiwan
[7] Tajen Univ, Dept Pharm, Pingtung 90741, Taiwan
[8] Tzu Hui Inst Technol, Dept Nursing, Pingtung 92641, Taiwan
来源
CHINESE JOURNAL OF PHYSIOLOGY | 2015年 / 58卷 / 05期
关键词
apoptosis; Ca2+; endoplasmic reticulum; human gastric cancer cells; phospholipase C; safrole; CARCINOGEN SAFROLE; INDUCED APOPTOSIS; PHASE ARREST; CALCIUM; INHIBITION; INCREASES; PROLIFERATION; ACTIVATION; INDICATORS; PATHWAYS;
D O I
10.4077/CJP.2015.BAD315
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Safrole is a carcinogen found in plants. The effect of safrole on cytosolic free Ca2+ concentrations ([Ca2+];) and viability in SCM1 human gastric cancer cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+](i). Safrole at concentrations of 150-450 iuM induced a [Ca2+]; rise in a concentration-dependent manner. The response was reduced by 60% by removing extracellular Ca2+. Safrole-evoked Ca2+ entry was not altered by nifedipine, econazole, SKF96365, and protein kinase C activator or inhibitor. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished safrole-evoked [Ca2+](i); rises. Conversely, treatment with safrole abolished thapsigargin or BHQ-evoked [Ca2+]; rises. Inhibition of phospholipase C (PLC) with U73122 abolished safrole-induced [Ca2+]; rises. At 250-550 RM, safrole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that safrole (350-550 ilM) induced apoptosis concentration-dependently. These studies suggest that in SCM1 human gastric cancer cells, safrole induced [Ca2+]; rises by inducing PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via non-store-operated Ca2+ entry pathways. Safrole-induced cell death may involve apoptosis.
引用
收藏
页码:302 / 311
页数:10
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