Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
Stelcer E. Komarowska H. Jopek K. Żok A. Iżycki D. Malińska A. Szczepaniak B. Komekbai Z. Karczewski M. Wierzbicki T. Suchorska W.M. Ruchała M. Ruciński M.
April 2022Spandidos Publications
Oncology Letters
2022#23Issue 4
A previous case report described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC), which was treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdrawal, suggesting a protective role for mitotane in a non-adrenal-derived tumor. The aim of the present study was to determine the biological response of primary melanoma cells obtained from that patient, and that of other established melanoma and ACC cell lines, to mitotane treatment using a proliferation assay, flow cytometry, quantitative PCR and microarrays. Although mitotane inhibited the proliferation of both ACC and melanoma cells, its role in melanoma treatment appears to be limited. Flow cytometry analysis and transcriptomic studies indicated that the ACC cell line was highly responsive to mitotane treatment, while the primary melanoma cells showed a moderate response in vitro. Mitotane modified the activity of several key biological processes, including mitotic nuclear division, DNA repair, angiogenesis and negative regulation of ERK1 and ERK2 cascade. Mitotane administration led to elevated levels of DNA double-strand breaks, necrosis and apoptosis. The present study provides a comprehensive insight into the biological response of mitotane-treated cells at the molecular level. Notably, the present findings offer new knowledge on the effects of mitotane on ACC and melanoma cells.
Adrenocortical carcinoma , Melanoma metastasis , Mitotane
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Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, 61-001, Poland
Radiobiology Laboratory, Greater Poland Cancer Centre, Poznan, 61-866, Poland
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, 60-355, Poland
Division of Philosophy of Medicine and Bioethics, Department of Social Sciences and Humanities, Poznan University of Medical Sciences, Poznan, 60-806, Poland
Department of Cancer Immunology, Poznan University of Medical Sciences, Poznan, 61-866, Poland
Department of Histology, West Kazakhstan Marat Ospanov Medical University, Aktobe, 030019, Kazakhstan
Department of General and Transplantation Surgery, Poznan University of Medical Sciences, Poznan, 60-355, Poland
Department of Endocrinological and Gastroenterological Surgery, Poznan University of Medical Sciences, Poznan, 60-355, Poland
Department of Histology and Embryology
Radiobiology Laboratory
Department of Endocrinology
Division of Philosophy of Medicine and Bioethics
Department of Cancer Immunology
Department of Histology
Department of General and Transplantation Surgery
Department of Endocrinological and Gastroenterological Surgery
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