Nonylphenol-induced apoptotic pathways in SCM1 human gastric cancer cells

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 NH₂-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 Ca²⁺ influx and intracellular Ca²⁺ 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 Ca²⁺-dependent apoptosis via the activation of p38 MAPK-associated caspase-3 in SCM1 cells.