期刊
MOLECULAR PHARMACEUTICS
卷 16, 期 3, 页码 1167-1183出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.8b01154
关键词
antitumor effects; apoptosis; ruthenium complex; transferrin; transferrin receptors; triple-negative breast cancer
资金
- Laboratory of Biology and Biochemistry (LBBM) from UFSCar
- National Counsel of Technological and Scientific Development - CNPq [2013/00798-2, 2015/24940-8, 2016/16312-0]
- Sao Paulo Research Foundation - FAPESP [2013/00798-2, 2015/24940-8, 2016/16312-0]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/00798-2] Funding Source: FAPESP
The triple-negative breast cancer subtype (TNBC) is highly aggressive and metastatic and corresponds to 15-20% of diagnosed cases. TNBC treatment is hampered, because these cells usually do not respond to hormonal therapy, and they develop resistance to chemotherapeutic drugs. On the other hand, the severe side effects of cisplatin represent an obstacle for its clinical use. Ruthenium (Ru)-based complexes have emerged as promising antitumor and antimetastatic substitutes for cisplatin. In this study, we demonstrated the effects of a Ru/biphosphine complex, containing gallic acid (GA) as a ligand, [Ru(GA)(dppe)(2)]PF6, hereafter called Ru(GA), on a TNBC cell line, and compared them to the effects in a nontumor breast cell line. Ru(GA) complex presented selective cytotoxicity against TNBC over nontumor cells, inhibited its migration and invasion, and induced apoptosis. These effects were associated with the increased amount of transferrin receptors (TfR) on tumor cells, compared to nontumor ones. Silencing of TfR decreased Ru(GA) effects on TNBC cells, demonstrating that these receptors were at least partially responsible for Ru(GA) delivery into tumor cells. The Ru(GA) compound must be further studied in different in vivo assays in order to investigate its antitumor properties and its toxicity in complex biological systems.
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