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; Chun-Jen Huang; Being-Whey Wang; Po-Min Chang; Yi-Chien Fang; Wei-Chuan Chen; Jue-Long Wang; Yih-Chau Lu; Sau-Tung Chu; Chiang-Ting Chou; Chung-Ren Jan

doi:10.1093/toxsci/kfm205

Thimerosal-induced apoptosis in human SCM1 gastric cancer cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation

Toxicol Sci. 2007 Nov;100(1):109-17. doi: 10.1093/toxsci/kfm205. Epub 2007 Aug 13.

Authors

Shiuh-Inn Liu¹, Chorng-Chih Huang, Chun-Jen Huang, Being-Whey Wang, Po-Min Chang, Yi-Chien Fang, Wei-Chuan Chen, Jue-Long Wang, Yih-Chau Lu, Sau-Tung Chu, Chiang-Ting Chou, Chung-Ren Jan

Affiliation

¹ Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.

PMID: 17698513
DOI: 10.1093/toxsci/kfm205

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracenes / pharmacology
Apoptosis / drug effects*
Calcium Signaling / drug effects*
Caspase 3 / metabolism*
Cell Line, Tumor
Cell Survival / drug effects
Chelating Agents / pharmacology
Dose-Response Relationship, Drug
Egtazic Acid / analogs & derivatives
Egtazic Acid / pharmacology
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / metabolism
Flavonoids / pharmacology
Humans
Imidazoles / pharmacology
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases / metabolism
Phosphorylation
Preservatives, Pharmaceutical / toxicity*
Protein Kinase Inhibitors / pharmacology
Pyridines / pharmacology
Stomach Neoplasms / enzymology
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology*
Thimerosal / toxicity*
Time Factors
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Anthracenes
Chelating Agents
Flavonoids
Imidazoles
Preservatives, Pharmaceutical
Protein Kinase Inhibitors
Pyridines
1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
pyrazolanthrone
Thimerosal
Egtazic Acid
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
CASP3 protein, human
Caspase 3
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one