Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06

• Published in: Pharmacological reports 2022-06, Vol.74 (3), p.545-554
• Main Authors: Duarte, Sâmia Sousa, Silva, Daiana Karla Frade, Lisboa, Thaís Mangeon Honorato, Gouveia, Rawny Galdino, de Andrade, Camyla Caroliny Neves, de Sousa, Valgrícia Matias, Ferreira, Rafael Carlos, de Moura, Ricardo Olimpio, Gomes, Joilly Nilce Santana, da Silva, Patricia Mirella, de Lourdes Assunção Araújo de Azevedo, Fátima, Keesen, Tatjana S. L., Gonçalves, Juan Carlos Ramos, Batista, Leônia Maria, Sobral, Marianna Vieira
• Format: Article
• Language: English
• Subjects: Drug Safety and Pharmacovigilance; Medicine; Pharmacotherapy; Pharmacy; Short Communication
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1007/s43440-022-00357-0

Background Acridine compounds have been described as promising anticancer agents. Previous studies showed that ( E )-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro. Methods MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC 50 ) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test. Results AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC 50 : 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak ( p