Sensitizing effects of cadmium on TNF-α- and TRAIL-mediated apoptosis of NIH3T3 cells with distinct expression patterns of p53

Byung Ju Kim, Mi Suk Kim, Ki Bae Kim, Kiwoo Kim, Yeon Mi Hong, In Ki Kim, Han Woong Lee, Yong Keun Jung

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Abstract

Tumor necrosis factor (TNF)-α and TNF-related apoptosis inducing ligand (TRAIL) share a common signaling pathway. Here we show a novel potentiating effect of cadmium on TNF-α- or TRAIL-mediated cell death via distinct signaling. TNF-α or TRAIL sensitized otherwise resistant NIH3T3 embryo fibroblast cells to death, when exposed to cadmium. The potentiating effects elicited by TNF-α or TRAIL on cell death were NF-κB- and SAPK/JNK-independent and were not diminished by the expression of Bcl 2. TNF-α potentiated the cadmium-induced accumulation of p53 but did not affect expression levels of Bax, Mdm2 and p21WAF/CIP. A similar pattern of p53 accumulation was also observed in Balbc/3T3 fibroblasts but not in human tumor cell lines, MCF7 and HeLa cells. The synergistic cell death evoked by TNF-α and cadmium was attenuated by transient expression of a dominant negative p53Val135 mutant in NIH3T3 cells and was not observed in p53(-/-) mouse embryo fibroblasts, indicating that p53 accumulation appears to contribute to cell death. In contrast, TRAIL did not further increase the cadmium-induced accumulation of p53 despite its potentiation effects on the cadmium-induced cell death. Expression of p53Val135 mutant did not reduce TRAIL- and cadmium-mediated cell death. Taken together, these results suggest that TNF-α and TRAIL potentiate the cadmium-mediated cell death via distinct p53 expression patterns.

Original languageEnglish
Pages (from-to)1411-1417
Number of pages7
JournalCarcinogenesis
Volume23
Issue number9
Publication statusPublished - 2002 Sep 1

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All Science Journal Classification (ASJC) codes

  • Cancer Research

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