Transport of the Ruthenium Complex [Ru(GA)(dppe)(2)]PF6 into Triple-Negative Breast Cancer Cells Is Facilitated by Transferrin Receptors

Autor(es)

Naves, Marina A. ^[1] ; Graminha, Angelica E. ^[1] ; Vegas, Legna C. ^[2] ; Luna-Dulcey, Liany ^[1] ; Honorato, Joao ^[2] ; Menezes, Antonio C. S. ^[3] ; Batista, Alzir A. ^[2] ; Cominetti, Marcia R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Lab Biol Aging LABEN, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, Lab Struct & React Inorgan Cpds LERCI, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

^[3] State Univ Goias, Campus Exact Sci & Technol CCET, BR-75132903 Anapolis, GO - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; v. 16, n. 3, p. 1167-1183, MAR 2019.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 16/16312-0 - Citotoxidade e mecanismo de ação de complexos de rutênio contendo produtos naturais ou derivados
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/24940-8 - Avaliação da eficácia de mudanças estruturais do [10]-gingerol em combinação com o quimioterápico doxorubicina para o tratamento de câncer de mama: estudos in vitro e in vivo
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/00798-2 - A matriz extracelular no envelhecimento, no exercício e no microambiente tumoral
• Beneficiário: Heloisa Sobreiro Selistre de Araújo
• Modalidade de apoio: Auxílio à Pesquisa - Temático