RT Journal Article
SR Electronic
T1 Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5049
OP 5057
DO 10.21873/anticanres.14508
VO 40
IS 9
A1 SÂMIA SOUSA DUARTE
A1 DAIANA KARLA FRADE SILVA
A1 THAÍS MANGEON HONORATO LISBOA
A1 RAWNY GALDINO GOUVEIA
A1 RAFAEL CARLOS FERREIRA
A1 RICARDO OLÍMPIO DE MOURA
A1 JAMIRE MURIEL DA SILVA
A1 ÉSSIA DE ALMEIDA LIMA
A1 SANDRA RODRIGUES-MASCARENHAS
A1 PATRICIA MIRELLA DA SILVA
A1 DAVI FELIPE FARIAS
A1 JULIANA ALVES DA COSTA RIBEIRO SOUZA
A1 KARINA CARLA DE PAULA MEDEIROS
A1 JUAN CARLOS RAMOS GONÇALVES
A1 MARIANNA VIEIRA SOBRAL
YR 2020
UL http://ar.iiarjournals.org/content/40/9/5049.abstract
AB 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.