Doxorubicin induces cytotoxicity and miR-132 expression in granulosa cells
| Autor: | Boodor Al-Kawlani, Udo R. Markert, Andreas Fritzsche, Simone Winkler, Karolin Fröhlich, José Martin Murrieta-Coxca, Diana M. Morales-Prieto, Wittaya Chaiwangyen |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system
Cell Survival 010501 environmental sciences Toxicology 01 natural sciences 03 medical and health sciences miR-132 Aromatase microRNA polycyclic compounds Humans Medicine Secretion Doxorubicin Viability assay Cytotoxicity Cells Cultured 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Antibiotics Antineoplastic Granulosa Cells Estradiol biology business.industry medicine.disease carbohydrates (lipids) MicroRNAs Leukemia Cancer research biology.protein Female business Biomarkers medicine.drug |
| Zdroj: | Reproductive Toxicology. 96:95-101 |
| ISSN: | 0890-6238 |
| Popis: | Doxorubicin (DOX) is one of the most commonly used drugs for the treatment of childhood cancers, including leukemia and lymphomas. Despite the high survival rate, female leukemia survivors are at higher risk of ovarian failure and infertility later in life. Treatment with chemotherapeutic drugs like DOX is associated with damage in ovarian follicles, but the affectation grade of granulosa cells remains unclear. To assess and avoid the possible side-effects of DOX, early biomarkers of ovarian injury and chemotherapy-induced ovarian toxicity should be identified. MicroRNAs (miRNAs) have emerged in recent years as a promising new class of biomarkers for drug-induced tissue toxicity. In this study, the effects of DOX on cell viability, steroidogenesis, and miRNA expression were studied in primary granulosa cells (GCs) and in two cellular models (COV434 and KGN cells). We report that compared to other chemotherapeutic drugs, DOX treatment is more detrimental to granulosa cells as observed by decrease of cell viability. Treatment with DOX changes the expression of the aromatase gene (CYP19A1) and the secretion of 17β-estradiol (E2) in a cell-specific manner. miR-132-3p is dose-dependently increased by DOX in all cellular models. In absence of DOX, miR-132-3p overexpression in COV434 cells has no effect on E2 secretion or CYP19A1 expression. Altogether, these findings contribute to understanding the hormonal disbalance caused by DOX in human ovarian cells and suggest miR-132 as a putative sensor to predict DOX-induced ovarian toxicity. |
| Databáze: | OpenAIRE |
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