In vitro chemo-preventive efficacy of synthetic progestin Norethindrone in human epithelial ovarian cancer.

Abstract

Progestin-only based oral contraceptives are majorly used as 'minipill' to prevent unintended pregnancy and treat conditions like polycystic ovary syndrome, hirsutism, and acne. However, the dearth of literature has constrained our comprehension of the exogenous progestin in relation to ovarian cancer progression. Therefore, the aim of the present study was to evaluate the chemo-preventive potential of synthetic progestin Norethindrone (NET) in epithelial ovarian cancer in vitro. Briefly, SKOV3 cells were treated with 1, 10 and 100µM concentrations of NET for seven days period. The assays for cell viability, wound-healing, cell cycle progression, detection of reactive oxygen species (ROS) and apoptosis were executed to illustrate the protective role of NET. To further clarify the underlying process, quantitative analysis of mRNA levels of oncogenes linked to angiogenesis, inflammation, proliferation, and metastasis (VEGF, HIF-1α, COX-2, and PGRMC1) and tumour suppressor (TP53) genes was conducted. Our study revealed that NET treatment significantly reduced SKOV3 cell growth by inducing cell cycle arrest at G2/M phase, elevating ROS levels, triggering cell death via apoptosis and necrosis, and inhibiting cell migration in a dose-dependent manner. Notably, NET also upregulated TP53 expression while concurrently downregulating VEGF, HIF-1α, COX-2, and PGRMC1 expression. Our results demonstrated that the chemo-preventive effect of Norethindrone may originate from the interaction of genes which exert a protective effect against ovarian carcinogenesis. The current findings also support further investigation, which may lead to changes in prescription practices or health-related advice for women.