LAUSR

Introduction/Background In postmenopausal women estrogen levels depend solely upon the local formation from steroid precursors, dehydroepiandrosterone-sulfate and estrone-sulfate (E1-S). Decreased estrogen levels are associated with menopausal symptoms, which often occur in peri- and postmenopausal women. Traditionally, hormone replacement therapy (HRT) has been prescribed to ease these symptoms. Due to the reported association with increased risk of breast cancer, stroke and pulmonary embolism the use of HRT has declined dramatically. Women are thus deciding for natural ‘HRT’, including extracts from Cimicifuga racemosa (CE). While CE treatment is considered as safe, little is known about its effects on endometrial or ovarian cancers, hormone-dependent malignancies that arise in this population of women. Methodology We aimed to evaluate the effects of CE (BNO 1055, a gift from Bionorica SE) on local formation of estradiol from the steroid precursor E1-S in the endometrial and ovarian cancer cell lines (CLs). We thus exposed poorly differentiated (KLE), and moderately differentiated (RL95-2) endometrial carcinoma, and high-serous ovarian carcinoma (COV362 and Kuramochi) CLs to CE and measured the effect on the expression of 13 E1-S transporter genes and 6 genes encoding estradiol biosynthetic and metabolic enzymes with RT-qPCR. Results The E1-S transporter genes were mainly upregulated upon CE treatment, with the highest differences seen for SLCO4A1 in KLE and COV362 CL. For genes involved in estradiol biosynthesis and metabolism we saw decreased as well as increased expression in individual CLs. The most significant upregulation was observed for HSD17B2 in KLE and downregulation for SULT1E1 in COV362. Interestingly, STS was significantly downregulated in all CLs. Genes encoding estrogen receptors ESR1 and ESR2 were significantly upregulated only in KLE. Conclusion Our research presents an insight of CE effects on endometrial or ovarian cancer CLs at the mRNA level. The effects at the protein level and the level of E1-S metabolism still needs to be evaluated. Disclosure Nothing to disclose.