Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition

Cell Biol Toxicol. 2017 Jun;33(3):251-261. doi: 10.1007/s10565-016-9368-3. Epub 2016 Oct 28.

Abstract

Exposure to compounds with cancer-potentiating effects can contribute to the progression of cancer. Herein we have discovered for the first time that benzophenone-3 (BP-3), a chemical used as sunscreen in various cosmetic products, enhances the ability of lung cancer cells to undergo metastasis. The exposure of the lung cancer cells to BP-3 at non-toxic concentrations significantly increased the number of anoikis resistant cells in a dose-dependent manner. Also, BP-3 increased the growth rate as well as the number of colonies accessed by anchorage-independent growth assay. We found that the underlying mechanisms of such behaviors were the epithelial to mesenchymal transition (EMT) process of cancer cells, and the increase in caveolin-1 (Cav-1) expression. As both mechanistic events mediated anoikis resistance via augmentation of cellular survival signals, our results further revealed that the BP-3 treatment significantly up-regulated extracellular-signal-regulated kinase (ERK). Also, such compounds increased the cellular levels of anti-apoptotic Bcl-2 and Mcl-1 proteins. As the presence of a substantial level of BP-3 in plasma of the consumers has been reported, this finding may facilitate further investigations that lead to better understanding and evidence concerning the safety of use in cancer patients.

Keywords: Anoikis resistance; Benzophenone-3 (BP-3); Epithelial to mesenchymal transition (EMT); Lung cancer cells; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Anoikis / drug effects
  • Benzophenones / adverse effects*
  • Caveolin 1 / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Lung
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Neoplasm Metastasis / pathology*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects

Substances

  • Benzophenones
  • Caveolin 1
  • Myeloid Cell Leukemia Sequence 1 Protein
  • oxybenzone
  • Extracellular Signal-Regulated MAP Kinases