Journal Article

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

SOBRAL, MARIANNA VIEIRA, DA COSTA RIBEIRO SOUZA, JULIANA ALVES, DE ALMEIDA LIMA, ÉSSIA, GONÇALVES, JUAN CARLOS RAMOS, SILVA, DAIANA KARLA FRADE, RODRIGUES-MASCARENHAS, SANDRA, DE PAULA MEDEIROS, KARINA CARLA, LISBOA, THAÍS MANGEON HONORATO, GOUVEIA, RAWNY GALDINO, DE MOURA, RICARDO OLÍMPIO, DA SILVA, PATRICIA MIRELLA, FARIAS, DAVI FELIPE, DA SILVA, JAMIRE MURIEL, DUARTE, SÂMIA SOUSA, FERREIRA, RAFAEL CARLOS

2020

Overview

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 (LD50 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-G1 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.

• Publisher: International Institute of Anticancer Research
• Subject: Acridine / Angiogenesis / Animals / Antiangiogenics / Anticancer properties / Antitumor activity / Apoptosis / Ascites / Cancer / Cell cycle / Cytokines / Danio rerio / Drug dosages / Eggs / Embryos / Genotoxicity / Immunomodulation / Software / Toxicity / Tumor cells / Tumor necrosis factor-α / Tumors / Zebrafish / γ-Interferon