Journal
SAUDI PHARMACEUTICAL JOURNAL
Volume 28, Issue 3, Pages 246-254Publisher
ELSEVIER
DOI: 10.1016/j.jsps.2020.01.003
Keywords
Hydantoin derivatives; Breast cancer cell line MDA-MB-231; Proliferation; Apoptosis; Cell motility; Nitric oxide
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Funding
- Ministry of Education and Science, and Technological Development of the Republic of Serbia [III41010, 175033, 173041]
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In this study, a series of synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives as a potential antiproliferative and antimigratory agents were investigated. The possible antitumor mechanisms of investigated hydantoin derivatives were examined on human breast cancer cell line MDA-MB-231. The cells were treated with different concentrations of compounds (from 0.01 mu M to 100 mu M) during 24 h and 72 h. The proliferation index, nitric oxide production, apoptosis rate, and migration capacity were measured. The cell invasion potential was examined by measuring the level of MMP-9 and COX-2 gene expression. All tested compounds expressed antiproliferative activity and induced dose- and time-dependent increase in the level of nitrites. The investigated molecules significantly decreased cell survival rate, migration capacity and the expression levels of genes included in the process of tumor invasion. Obtained data suggest that the tested hydantoin derivatives express considerable antitumor activity by reducing cell division rate, elevating apoptosis level, and inhibiting the motility and invasiveness of breast cancer cells. The results obtained in this study indicate that investigated compounds express potential as a novel chemotherapeutic agents against breast cancer growth and progression. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.
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