Raffaella Fabbri1, Maria Macciocca1, Rossella Vicenti1, Roberto Paradisi1, Francesca Gioia Klinger2, Gianandrea Pasquinelli3, Enzo Spisni4, Renato Seracchioli1, Alessio Papi4. 1. Gynecology & Pathophysiology of Human Reproductive Unit, Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy. 2. Department of Biomedicine & Prevention, University of Rome Tor Vergata, Rome, Italy. 3. Surgical Pathology, Department of Experimental, Diagnostic & Speciality Medicine, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy. 4. Department of Biological, Geological, & Environmental Science, University of Bologna, Bologna, Italy.
Abstract
AIM: To investigate mechanisms by which doxorubicin (DOX) and cisplatin (CIS) cause human ovarian stroma injury. PATIENTS & METHODS: Stromal cells from human cryopreserved ovarian tissue were cultured in the presence of 1 µM DOX and 10 µM CIS. Ovarian damage induced by treatments was evaluated by 'Live/Dead' and sulforhodamine-B assays, the expression of different apoptosis markers. RESULTS: Stromal cell growth was inhibited by DOX and CIS, and this effect was accompanied by apoptosis through mitochondrial pathway activation: Bax, cleaved-caspase 9, cleaved-PARP1 induction and Akt1, Bcl2, phospho-44/42-MAPK/ERK1/2 reduction were observed. CONCLUSION: DOX and CIS induced apoptosis in human ovarian stromal cells. Knowledge of mechanisms by which the drugs act is important to identify possible ways to counteract side effects of chemotherapy on ovaries.
AIM: To investigate mechanisms by which doxorubicin (DOX) and cisplatin (CIS) cause humanovarian stroma injury. PATIENTS & METHODS: Stromal cells from human cryopreserved ovarian tissue were cultured in the presence of 1 µM DOX and 10 µM CIS. Ovarian damage induced by treatments was evaluated by 'Live/Dead' and sulforhodamine-B assays, the expression of different apoptosis markers. RESULTS: Stromal cell growth was inhibited by DOX and CIS, and this effect was accompanied by apoptosis through mitochondrial pathway activation: Bax, cleaved-caspase 9, cleaved-PARP1 induction and Akt1, Bcl2, phospho-44/42-MAPK/ERK1/2 reduction were observed. CONCLUSION:DOX and CIS induced apoptosis in human ovarian stromal cells. Knowledge of mechanisms by which the drugs act is important to identify possible ways to counteract side effects of chemotherapy on ovaries.
Entities:
Keywords:
cisplatin; doxorubicin; human ovarian stromal cells
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