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Pro-apoptotic and anti-migration properties of a thiazoline-containing platinum(II) complex in MDA-MB-231 breast cancer cells: role of melatonin as synergistic agent

Triple-negative breast cancer (TNBC) is an aggressive cancer that does not respond to hormonal and HER2-targeted therapies and have poor prognosis. Therefore, there is a need for the development of convenient anticancer strategies that can be effectively used for the treatment of TNBC. Herein, we evaluated the antitumoral potential of a platinum(II) complex coordinated with the ligand 2-(3,5-diphenylpyrazol-1-yl)-2-thiazoline (DPhPzTn), hereafter PtDPhPzTn, against the TNBC cell line MDA-MB-231. The potentiating actions of melatonin on the tumor-killing ability of PtDPhPzTn were also checked in MDA-MB-231 cells. We first examined the cytotoxic effect of both PtDPhPzTn and melatonin in the TNBC cells, which were dose-dependent. We then combined different doses of PtDPhPzTn and melatonin to test their combinatorial effect and found a synergistic effect, especially when combining 1 mM melatonin and 5, 10 and 25 µM PtDPhPzTn. Additionally, PtDPhPzTn induced apoptosis mediated by caspase-3/-9 activation and dependent on reactive oxygen species overproduction. Likewise, PtDPhPzTn almost completely blunted the migration capacity of MDA-MB-231 cells. Combined treatment with PtDPhPzTn and melatonin moderately potentiated the pro-apoptotic and anti-migratory actions of the complex alone. These findings suggest that aromatic groups improve the cytotoxicity of the compound and provide evidence that PtDPhPzTn and melatonin could be potentially applied to TBNC treatment as synergistic agents.

Keywords: Breast cancer, Caspases, Cytotoxicity, Melatonin, Platinum(II) complex