Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions.

Autor: Duarte SS; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Silva DKF; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Lisboa TMH; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Gouveia RG; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., Ferreira RC; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil., DE Moura RO; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, Brazil., DA Silva JM; Post Graduation Program in Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil., DE Almeida Lima É; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, Brazil., Rodrigues-Mascarenhas S; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil.; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, Brazil., DA Silva PM; Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Brazil., Farias DF; Laboratory of Risk Assessment for Novel Technologies, Department of Molecular Biology, Federal University of Paraiba, João Pessoa, Brazil., DA Costa Ribeiro Souza JA; Laboratory of Risk Assessment for Novel Technologies, Department of Molecular Biology, Federal University of Paraiba, João Pessoa, Brazil., DE Paula Medeiros KC; Department of Morphology, Federal University of Rio Grande do Norte, Natal, Brazil., GonÇalves JCR; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil., Sobral MV; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Brazil mariannavbs@gmail.com.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil.
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2020 Sep; Vol. 40 (9), pp. 5049-5057.
DOI: 10.21873/anticanres.14508
Abstrakt: Background/aim: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound.
Materials and Methods: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated.
Results: AMTAC-06 did not induce toxicity on zebrafish and mice (LD 50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G 1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1β and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals.
Conclusion: AMTAC-06 has low toxicity and a significant antitumor activity.
(Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze: MEDLINE
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