Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells.

Archives of Toxicology
Durr-E-Shahwar MalikNigel J Gooderham

Abstract

Benzo[a]pyrene (B(a)P) is a major cancer-causing contaminant present in food such as cooked meats and cereals, and is ubiquitous in the environment in smoke derived from the combustion of organic material. Exposure to B(a)P is epidemiologically linked with the incidence of breast cancer. Although B(a)P is recognized as a complete genotoxic carcinogen, thought to act primarily via CYP-mediated metabolic activation to DNA-damaging species, there is also evidence that B(a)P exposure elicits other biological responses that promote development of the cancer phenotype. Here in mechanistic studies using human mammary cells MCF-7 and MDA-MB-231, we have explored mechanisms whereby B(a)P (10- 8 to 10- 5M) promotes inflammation pathways via TNF-α and NFκB leading to IL-6 upregulation, microRNA (Let7a, miR21 and miR29b) dysregulation and activation of VEGF. The miRNA dysregulation is associated with altered expression of inflammation mediators and increased migration and invasive potential of human mammary cancer cells. Our data suggest that mammary cell exposure to B(a)P results in perturbation of inflammation mediators and dysregulation of tumorigenic miRNAs, leading to an inflammation microenvironment that facilitates migration and inv...Continue Reading

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Citations

Jul 11, 2019·Cell Communication and Signaling : CCS·Wang-Yu CaiQi-Cong Luo
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Anna FishbeinDipak Panigrahy
Nov 13, 2019·Epigenetics & Chromatin·Dandan ZongPing Chen
Aug 18, 2021·Environmental Science and Pollution Research International·Rupa RaniRajesh Ahirwar
Sep 3, 2021·BMC Complementary Medicine and Therapies·Sung-Yong HongMihi Yang

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Methods Mentioned

BETA
transfection

Software Mentioned

GraphPad
GraphPad Prism
Image J

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