Effect of nonylphenol on the regulation of cell growth in colorectal cancer cells

Nonylphenol (NP) is a well-known endocrine-disrupting chemical (EDC), which can enhance the progression of cancer by functioning as an estrogen-like factor. In the present study, the effects of different concentrations of NP on COLO205 colorectal cancer (CRC) cells were examined. The results of flow cytometric analysis revealed that NP significantly decreased the proportion of cells in the G(0)/G(1) phase in a dose-dependent manner, which was accompanied by a marginal increase in the proportions of cells in S and G2/M phases. NP did not induce apoptosis, whereas estradiol (E2) did induce apoptosis. To elucidate the mechanisms underlying the action of NP on COLO205 cells, the transcriptional levels of extracellular signal-regulated kinase (ERK) 1, ERK2 and phosphoinositide 3-kinase (PI3K) were assessed using reverse transcription-quantitative polymerase chain reaction analysis. The expressions levels of ERK1, ERK2 and PI3K were increased by treatment with NP in a dose-dependent manner. On examining protein levels, the expression of PI3K p38 was increased by NP and E2, and the expression of ERK1/2 was increased by NP. The phosphorylation of the ERK protein was significantly increased by treatment with NP at a high concentration (10-4 M; P<0.01), but significantly decreased by E2 (P<0.01). Two key proteins in the transforming growth factor (TGF) beta pathway (c-Fos and SnoN) were selected for analysis using western blot analysis in the COLO205 cells treated with NP and E2. The expression levels of c-Fos and SnoN were significantly increased by treatment with E2 (10(-7) M; P<0.01) and NP (10-7-10-4 M; P<0.01). Taken together, these results indicated that NP affected the development of CRC via the ERK signaling pathway and TGF beta pathway.