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Nonylphenol‐induced apoptotic pathways in SCM1 human gastric cancer cells
Author(s) -
Kuo ChunChi,
Kuo DaihHuang,
Huang ChunJen,
Fang YiChien,
Shieh Pochuen,
Chen FuAn,
Shaw ChenFu,
Jan ChungRen
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20355
Subject(s) - nonylphenol , mapk/erk pathway , kinase , apoptosis , protein kinase a , p38 mitogen activated protein kinases , microbiology and biotechnology , chemistry , propidium iodide , extracellular , programmed cell death , biology , biochemistry , environmental chemistry
Abstract Environmental chemicals may affect human health by disrupting endocrine function. Many endocrine disrupting chemicals (EDCs) are estrogen‐like molecules that are classified as xenoestrogens (XEs). One XE, nonylphenol, is used as a surfactant or plasticizer and exhibits biotoxicity when accumulated in the body via the food chain. The aim of the present study was to clarify the role of nonylphenol‐induced SCM1 apoptosis by measuring cultured human gastric cancer cell (SCM1) death. Using WST‐1 reduction and propidium iodide‐staining assays, nonylphenol treatment was found to activate caspase‐3 and mitogen‐activated protein kinases (MAPKs), major markers in apoptotic pathways. Nonylphenol also activated the phosphorylation of extracellular signal‐regulated kinase (ERK), c‐Jun NH 2‐ terminal kinase (JNK), and p38 mitogen‐activated protein kinase (p38 MAPK). However, only SB203580 (a p38MAPK inhibitor) partially inhibited nonylphenol‐induced apoptosis. Nonylphenol induced a [Ca 2+ ] i rise by causing extracellular Ca 2+ influx and intracellular Ca 2+ release from the endoplasmic reticulum, and its effects on SCM1 cell death were prevented by pretreatment with the Ca 2+ chelator BAPTA/AM. These results suggest that nonylphenol caused Ca 2+ ‐dependent apoptosis via the activation of p38 MAPK‐associated caspase‐3 in SCM1 cells. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc.