Polyphenol inhibition of benzo[a]pyrene-induced oxidative stress and neoplastic transformation in an in vitro model of carcinogenesis

Food Chem Toxicol. 2017 Aug;106(Pt A):165-174. doi: 10.1016/j.fct.2017.05.037. Epub 2017 May 19.

Abstract

While dietary polyphenols are widely recognized for cancer-preventing characteristics, the relative effectiveness and mechanisms of action of different polyphenols is not clear. In the present study, we investigated the protective effects of six different polyphenols against benzo[a]pyrene (B[a]P)-induced oxidative stress and neoplastic transformation in the Bhas 42 cell carcinogenesis assay. All of the polyphenols completely prevented the increased intracellular ROS generation by B[a]P at 12 h, and most inhibited after 3 days. B[a]P increased mitochondrial superoxide generation at 12 h, which was inhibited by the anthocyanins and berberine. B[a]P increased expression of genes related to oxidative stress and inflammation (Nrf2, UCP2, and TNF-α) after 24 h. Polyphenols strongly inhibited the increase in TNF-α and also several polyphenols inhibited the increase in UCP2. At 21 days after 72 h treatment, B[a]P produced a large increase in the number of neoplastic colonies. This transformation was inhibited by most polyphenols, and strongly by resveratrol. In summary, all tested polyphenols were able to inhibit B[a]P-induced increases in markers of oxidative stress and inflammation, and to inhibit cellular transformation, with resveratrol being notable for the strongest preventive effect on cell transformation. The results support a role for dietary polyphenols in protecting against B[a]P-induced carcinogenesis.

Keywords: Benzo [a]pyrene; Carcinogenesis; Mitochondrial reactive oxygen species; Neoplastic transformation; Oxidative stress; Polyphenols.

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • Carcinogenesis / drug effects*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects*
  • Humans
  • Mice
  • Models, Biological
  • Oxidative Stress / drug effects*
  • Polyphenols / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Polyphenols
  • Tumor Necrosis Factor-alpha
  • Benzo(a)pyrene