Endocrine-disruptor chemicals (EDCs), such as Bisphenol A ( ) and (NP), have been widely studied due to their negative effects on human and wildlife reproduction. Exposure to or NP is related to cell death, hormonal deregulation, and cancer onset. Our previous studies showed that both compounds induce A Disintegrin And Metalloprotease 17 (ADAM17) activation. Here, we show that and NP induce apoptosis in prostate and ovary cancer cell lines, in a process dependent on ADAM17 activation. ADAM17 knockdown completely prevented apoptosis as well as the shedding of ADAM17 substrates. Both compounds were found to induce an increase in intracellular calcium (Ca < sup > 2+ < /sup >) only in Ca < sup > 2+ < /sup > -containing medium, with the NP-treated cells response being more robust than those treated with . Additionally, using a phosphorylated protein microarray, we found that both compounds stimulate common intracellular pathways related to cell growth, differentiation, survival, and apoptosis. These results suggest that and NP could induce apoptosis through ADAM17 by activating different intracellular signaling pathways that may converge in different cellular responses, one of which is apoptosis. These results confirm the capacity of these compounds to induce cell apoptosis in cancer cell lines and uncover ADAM17 as a key regulator of this process in response to EDCs.
Liu Y., Liang Y., Wishart D.S. (2015) PolySearch 2.0: A significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins, and more. Nucleic Acids Res. 2015 Jul 1;43(Web Server Issue):W535-42.
Cheng D., Knox C., Young N., Stothard P., Damaraju S., Wishart D.S. (2008) PolySearch: a web-based text mining system for extracting relationships between human diseases, genes, mutations, drugs and metabolites. Nucleic Acids Res. 2008 Jul 1;36(Web Server Issue):W399-405.
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.