Abstract

<h3>Introduction/Background*</h3> In postmenopausal women estrogen levels depend exclusively upon the local formation from steroid precursors dehydroepiandrosterone-sulfate and estrone-sulfate (E1-S). The reduced estrogen levels are associated with menopausal symptoms, which often occur in peri- and postmenopausal patients. To mitigate these symptoms nowadays more women choose medicine of natural origin, e.g. extracts from <i>Cimicifuga racemose</i> (CE) instead of hormone replacement therapy, which is associated with increased risk of breast cancer, stroke and pulmonary embolism. While CE treatment is considered as safe, little is known about its effects on healthy endometrial or ovarian tissue and even less on hormone-dependent malignancies like endometrial and ovarian cancer that arise in this population of women. The aim of our study was to examine the influence of CE on the expression of genes encoding E1-S transporters and estrogen biosynthetic and metabolic enzymes in control and cancerous endometrial and ovarian cell lines. <h3>Methodology</h3> Control endometrial cell line (HIEEC), control ovarian cell line (HIO80) and cell lines of well differentiated endometrial carcinoma (Ishikawa and HEC-1-A), moderately differentiated adenosquamous carcinoma (RL-95-2), poorly differentiated endometrial carcinoma (KLE) and high grade ovarian serous adenocarcinoma (Kuramochi, COV62 and OVSAHO) were exposed to CE in different concentrations for 72h. The expression of 9 E1-S transporter genes (<i>SLCO4C1, SLC51A, ABCC1, ABCC4, SLC10A6, SLCO1A2, SLCO2B1, SLCO3A1, SLCO4A1</i>) and 4 genes encoding estrogen biosynthetic/metabolic enzymes (<i>HSD17B1, HSD17B2, STS and SULT1E1</i>) and estrogen receptors (<i>ESR1</i> and <i>ESR2</i>) were measured using RT-qPCR. <h3>Result(s)*</h3> The results revealed that CE affects the expression of genes encoding E1-S transporters and estrogen biosynthetic and metabolic enzymes only at very high concentrations of CE (50μg/ml or 100μg/ml), while no changes in expression were observed with concentrations that are similar to those detected in plasma of CE users. <h3>Conclusion*</h3> Our research presents an insight of CE effects on endometrial or ovarian cancer CLs at the mRNA level showing additional proof of safe usage of CE in healthy women and women with hormone-dependent malignancies like endometrial and ovarian cancer.

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