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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The trans-[Ru(PPh3)(2)(N,N-dimethyl-N `-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

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Autor(es):
Becceneri, Amanda Blanque [1] ; Popolin, Cecilia Patricia [1] ; Maria Plutin, Ana [2] ; Maistro, Edson Luis [3] ; Castellano, Eduardo Ernesto [4] ; Batista, Alzir Azevedo [5] ; Cominetti, Marcia Regina [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed Sao Carlos, Dept Gerontol, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil
[2] Univ Habana, Fac Quim, Zapata S-N Entre G & Carlitos Aguirre, Havana 10400 - Cuba
[3] Univ Estadual Paulista, Fac Filosofia & Ciencias, Dept Fonoaudiol, Av Hygino Muzzi Filho 737, BR-17525900 Marilia, SP - Brazil
[4] Univ Sao Paulo, Inst Fis Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP - Brazil
[5] Univ Fed Sao Carlos, Dept Quim, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Journal of Inorganic Biochemistry; v. 186, p. 70-84, SEP 2018.
Citações Web of Science: 2
Resumo

Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-{[}Ru (PPh3)(2)(N,N-dibutyl-N'-benzoylthioureato-k(2)O,S)(2,2'-bipyridine (bipy))]PF6 (1), trans-{[}Ru(PPh3)(2)(N,N-dimethyl-N'-thiophenylthioureato-k(2)O,S)(bipy) PF6 (2) and trans-{[}Ru(PPh3)(2)(N,N-dimethyl-N'-benzoylthioureatok(2)O,S)(bipy)]PF6 (3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice. (AU)

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
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/25121-8 - Atividade antitumoral e potencial mutagênico de novos complexos de rutênio
Beneficiário:Amanda Blanque Becceneri
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/00798-2 - A matriz extracelular no envelhecimento, no exercício e no microambiente tumoral
Beneficiário:Heloisa Sobreiro Selistre de Araújo
Linha de fomento: Auxílio à Pesquisa - Temático