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ToxSci Advance Access originally published online on August 13, 2007
Toxicological Sciences 2007 100(1):109-117; doi:10.1093/toxsci/kfm205
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Thimerosal-Induced Apoptosis in Human SCM1 Gastric Cancer Cells: Activation of p38 MAP Kinase and Caspase-3 Pathways without Involvement of [Ca2+]i Elevation

Shiuh-Inn Liu*, Chorng-Chih Huang{dagger}, Chun-Jen Huang{ddagger},§, Being-Whey Wang*, Po-Min Chang*, Yi-Chien Fang, Wei-Chuan Chen||, Jue-Long Wang|||, Yih-Chau Lu||||, Sau-Tung Chu#, Chiang-Ting Chou** and Chung-Ren Jan**,1

* Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813 {dagger} Department of Nursery, Tzu Hui Institute of Technology, Pingtung, Taiwan 926 {ddagger} Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 807 § Department of Psychiatry, Tian-Sheng Memorial Hospital, Ping-Tong, Taiwan 900 Laboratory Medicine Division, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan 813 || Department of Surgery, Ping Tung Christian Hospital, Ping Tung, Taiwan 900 ||| Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813 |||| Department of Orthopaedic Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813 # Department of Otolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813 ** Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813

1 To whom correspondence should be addressed. Fax: 886-7-3468056. E-mail: crjan{at}isca.vghks.gov.tw.

Received May 15, 2007; accepted July 20, 2007


  Abstract

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concentration- and time-dependent manner. Thimerosal caused apoptosis as assessed by propidium iodide–stained cells and caspase-3 activation. Although immunoblotting data revealed that thimerosal could activate the phosphorylation of extracellular signal–regulated kinase, c-Jun NH2-terminal protein kinase, and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Thimerosal also induced [Ca2+]i increases via Ca2+ influx from the extracellular space. However, pretreatment with (bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate)/AM, a Ca2+ chelator, to prevent thimerosal-induced [Ca2+]i increases did not protect cells from death. The results suggest that in SCM1 cells, thimerosal caused Ca2+-independent apoptosis via phosphorylating p38 MAPK resulting in caspase-3 activation.

Key Words: apoptosis; caspase-3; gastric cancer cells; MAPKs; thimerosal.


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L. Kuo, C. Huang, Y. Fang, C. Huang, J. Wang, K. Lin, S. Chu, H. Chang, J. Chien, H. Su, et al.
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[Abstract] [PDF]


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