TY - JOUR T1 - Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions JF - Anticancer Research JO - Anticancer Res SP - 5049 LP - 5057 DO - 10.21873/anticanres.14508 VL - 40 IS - 9 AU - SÂMIA SOUSA DUARTE AU - DAIANA KARLA FRADE SILVA AU - THAÍS MANGEON HONORATO LISBOA AU - RAWNY GALDINO GOUVEIA AU - RAFAEL CARLOS FERREIRA AU - RICARDO OLÍMPIO DE MOURA AU - JAMIRE MURIEL DA SILVA AU - ÉSSIA DE ALMEIDA LIMA AU - SANDRA RODRIGUES-MASCARENHAS AU - PATRICIA MIRELLA DA SILVA AU - DAVI FELIPE FARIAS AU - JULIANA ALVES DA COSTA RIBEIRO SOUZA AU - KARINA CARLA DE PAULA MEDEIROS AU - JUAN CARLOS RAMOS GONÇALVES AU - MARIANNA VIEIRA SOBRAL Y1 - 2020/09/01 UR - http://ar.iiarjournals.org/content/40/9/5049.abstract N2 - 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. ER -