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

Autor: Duarte SS; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Silva DKF; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Lisboa TMH; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Gouveia RG; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., de Andrade CCN; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., de Sousa VM; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Ferreira RC; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., de Moura RO; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, Paraíba, Brazil., Gomes JNS; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, Paraíba, Brazil., da Silva PM; Invertebrate Immunology and Pathology Laboratory, Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., de Lourdes Assunção Araújo de Azevedo F; Cardiovascular Pharmacology Laboratory, Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Keesen TSL; Immunology of Infectious Diseases Laboratory, Biotechnology Center, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Gonçalves JCR; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Batista LM; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil., Sobral MV; Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. mariannavbs@ltf.ufpb.br.; Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. mariannavbs@ltf.ufpb.br.; Laboratório de Oncofarmacologia (Oncofar), Instituto de Pesquisa em Fármacos e Medicamentos (IPeFarM). Cidade Universitária, Campus I, João Pessoa, Paraíba, 58051-900, Brazil. mariannavbs@ltf.ufpb.br.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2022 Jun; Vol. 74 (3), pp. 545-554. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1007/s43440-022-00357-0
Abstrakt: 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 < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001).
Conclusions: AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.
(© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)
Databáze: MEDLINE