Molecular Basis Supporting the Association of Talcum Powder Use With Increased Risk of Ovarian Cancer
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Molecular Basis Supporting the Association of Talcum Powder Use With Increased Risk of Ovarian Cancer
Reproductive Sciences 1-10 ยช The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119831773 journals.sagepub.com/home/rsx
Nicole M. Fletcher, PhD1, Amy K. Harper, MD2, Ira Memaj, BS1, Rong Fan, MS1, Robert T. Morris, MD2, and Ghassan M. Saed, PhD1,2
Abstract Genital use of talcum powder and its associated risk of ovarian cancer is an important controversial topic. Epithelial ovarian cancer (EOC) cells are known to manifest a persistent prooxidant state. Here we demonstrated that talc induces significant changes in key redox enzymes and enhances the prooxidant state in normal and EOC cells. Using real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, levels of CA-125, caspase-3, nitrate/nitrite, and selected key redox enzymes, including myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GSR), were determined. TaqMan genotype analysis utilizing the QuantStudio 12K Flex was used to assess single-nucleotide polymorphisms in genes corresponding to target enzymes. Cell proliferation was determined by MTT proliferation assay. In all talc-treated cells, there was a significant dose-dependent increase in prooxidant iNOS, nitrate/nitrite, and MPO with a concomitant decrease in antioxidants CAT, SOD, GSR, and GPX (P < .05). Remarkably, talc exposure induced specific point mutations that are known to alter the activity in some of these key enzymes. Talc exposure also resulted in a significant increase in inflammation as determined by increased tumor marker CA-125 (P < .05). More importantly, talc exposure significantly induced cell proliferation and decreased apoptosis in cancer cells and to a greater degree in normal cells (P < .05). These findings are the first to confirm the cellular effect of talc and provide a molecular mechanism to previous reports linking genital use to increased ovarian cancer risk. Keywords talc, epithelial ovarian cancer, oxidative stress, single-nucleotide polymorphism, cell proliferation
Introduction Ovarian cancer is the most lethal gynecologic malignancy and ranks fifth in cancer deaths among women diagnosed with cancer.1 Epithelial ovarian cancer (EOC) has long been considered a heterogeneous disease with respect to histopathology, molecular biology, and clinical outcome.1,2 Although surgical techniques and treatments have advanced over the years, the prognosis of EOC remains poor, with a 5-year survival rate of 50% in advanced stage.2 This is largely due to the lack of early warning symptoms and screening methods and the development of chemoresistance.1,2 Moreover, ovarian cancer is known to be associated with germline mutations in the BRCA1 or BRCA2 genes, but with a rate of only 20 % to 40%, suggesting the presence of other unknown mutations in other predisposition genes. 3 Additional genetic
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