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Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action.
Silva, Daiana K Frade; Duarte, Sâmia S; Lisboa, Thaís M H; Ferreira, Rafael C; Lopes, Ana Luíza de O; Carvalho, Deyse C M; Rodrigues-Mascarenhas, Sandra; da Silva, Patricia Mirella; Segundo, Miguel A S Pinheiro; Moura, Ricardo O de; Medeiros, Karina C P; Sobral, Marianna V.
Afiliação
  • Silva DKF; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Duarte SS; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Lisboa TMH; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Ferreira RC; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Lopes ALO; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Carvalho DCM; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Rodrigues-Mascarenhas S; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • da Silva PM; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Segundo MASP; Department of Molecular Biology, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.
  • Moura RO; Post Graduation Program in Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE 50670-901, Brazil.
  • Medeiros KCP; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, PB 58070-450, Brazil.
  • Sobral MV; Department of Morphology, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil.
Molecules ; 25(1)2019 Dec 20.
Article em En | MEDLINE | ID: mdl-31861795
Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1ß, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acridinas / Carcinoma de Ehrlich / Regulação Neoplásica da Expressão Gênica / Regulação para Cima / Células Th1 / Inibidores da Angiogênese / Antineoplásicos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acridinas / Carcinoma de Ehrlich / Regulação Neoplásica da Expressão Gênica / Regulação para Cima / Células Th1 / Inibidores da Angiogênese / Antineoplásicos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça