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

Mol Med Rep. 2017 Aug;16(2):2211-2216. doi: 10.3892/mmr.2017.6817. Epub 2017 Jun 20.

Abstract

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 G0/G1 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)β 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 TGFβ pathway.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Endocrine Disruptors / pharmacology*
  • Estradiol / pharmacology
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phenols / pharmacology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / drug effects

Substances

  • Endocrine Disruptors
  • Intracellular Signaling Peptides and Proteins
  • Phenols
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • SKIL protein, human
  • Transforming Growth Factor beta
  • Estradiol
  • nonylphenol
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3