The tyrosine kinase inhibitor nilotinib is more ef... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The tyrosine kinase inhibitor nilotinib is more efficient than mitotane in decreasing cell viability in spheroids prepared from adrenocortical carcinoma cells

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Author(s):
Silveira, Elaine [1] ; Cavalcante, Isadora Pontes [1] ; Kremer, Jean Lucas [1] ; Ribeiro de Mendonca, Pedro Omori [1] ; Pacicco Lotfi, Claudimara Ferini [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: CANCER CELL INTERNATIONAL; v. 18, MAR 1 2018.
Web of Science Citations: 2
Abstract

Background: New disease progression despite surgery and adjuvant therapy with mitotane. In this study, we aimed to investigate the in vitro effects of different chemotherapy drugs, alone or combined with mitotane, on the viability of adrenocortical carcinoma cells. Methods: Everolimus, sunitinib, zoledronic acid, imatinib and nilotinib cytotoxicity, alone or combined with mitotane were tested on ACC H295R cells in monolayer or spheroid cultures using MTS assays and confocal microscopy. Moreover, the nilotinib effects were investigated in spheroids cultured from patient tumor-derived ACC-T36 cells. Results: Morphological characterization of H295R cell spheroids using histochemistry was performed and showed that dense, homogenously sized, multicellular spheroids were obtained. We observed that sunitinib and nilotinib alone were equally effective in a monolayer preparation, whereas mitotane was the most effective even at a low dose. A combination of sunitinib and mitotane was the most effective treatment, with only 23.8% of cells in the monolayer remaining viable. Spheroid preparations showed resistance to different drugs, although the poor effect produced by mitotane alone was surprising, with a cell viability of 84.6% in comparison with 13.1% in monolayer cells. The most ineffective drugs in spheroid preparations were everolimus, zoledronic acid and imatinib. In both cell types, nilotinib, either alone or in combination with mitotane induced more significant cell viability inhibition in monolayer and spheroid preparations. In addition, the mechanism of nilotinib activity involves the ERK1/2 pathway. Conclusion: Taken together, our data identified nilotinib as a cytotoxic drug that combined with ERK inhibitors deserves to be tested as a novel therapy for adrenocortical carcinoma. (AU)

FAPESP's process: 11/07656-3 - Study the regulation of transcription factors SF-1 and LRH-1 in normal and tumor adrenal cells
Grantee:Claudimara Ferini Pacicco Lotfi
Support Opportunities: Regular Research Grants