Sâmia Sousa Duarte1, Daiana Karla Frade Silva1, Thaís Mangeon Honorato Lisboa1, Rawny Galdino Gouveia1, Camyla Caroliny Neves de Andrade1, Valgrícia Matias de Sousa1, Rafael Carlos Ferreira1, Ricardo Olimpio de Moura2, Joilly Nilce Santana Gomes2, Patricia Mirella da Silva3, Fátima de Lourdes Assunção Araújo de Azevedo4, Tatjana S L Keesen5, Juan Carlos Ramos Gonçalves6, Leônia Maria Batista1,6, Marianna Vieira Sobral7,8,9. 1. Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 2. Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, Paraíba, Brazil. 3. Invertebrate Immunology and Pathology Laboratory, Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 4. Cardiovascular Pharmacology Laboratory, Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 5. Immunology of Infectious Diseases Laboratory, Biotechnology Center, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 6. Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. 7. Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. mariannavbs@ltf.ufpb.br. 8. Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil. mariannavbs@ltf.ufpb.br. 9. 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.
Abstract
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 (IC50) 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 (IC50: 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.
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 (IC50) 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 (IC50: 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.
Authors: Sinara Mônica Vitalino de Almeida; Elizabeth Almeida Lafayette; Willams Leal Silva; Vanessa de Lima Serafim; Thais Meira Menezes; Jorge Luiz Neves; Ana Lucia Tasca Gois Ruiz; João Ernesto de Carvalho; Ricardo Olímpio de Moura; Eduardo Isidoro Carneiro Beltrão; Luiz Bezerra de Carvalho Júnior; Maria do Carmo Alves de Lima Journal: Int J Biol Macromol Date: 2016-07-18 Impact factor: 6.953
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702