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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines

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Autor(es):
Vital, Wagner D. [1] ; Torquato, Heron F. V. [2] ; Passos Jesus, Larissa de Oliveira [1] ; de Souza Judice, Wagner Alves [1] ; da Silva, Maria Fatima das G. F. [3] ; Rodrigues, Tiago [4] ; Justo, Giselle Zenker [5] ; Veiga, Thiago A. M. [6] ; Paredes-Gamero, Edgar J. [2, 7]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, Mogi das Cruzes - Brazil
[2] Univ Braz Cubas, Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo - Brazil
[3] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil
[4] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre - Brazil
[5] Univ Fed Sao Paulo, Dept Biol, Diadema - Brazil
[6] Univ Fed Sao Paulo, Dept Quim, Diadema - Brazil
[7] Univ Fed Mato Grosso do Sul, Fac Ciencias Farmaceut Alimentos & Nutr, Ave Costa E Silva S-N, BR-79070900 Campo Grande, MS - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Biochemistry; v. 120, n. 6, p. 9608-9623, JUN 2019.
Citações Web of Science: 1
Resumo

Several molecules extracted from natural products exhibit different biological activities, such as ion channel modulation, activation of signaling pathways, and anti-inflammatory or antitumor activity. In this study, we tested the antitumor ability of natural compounds extracted from the Raputia praetermissa plant. Among the compounds tested, an alkaloid, here called compound S4 (4-Deoxyraputindole C), showed antitumor effects against human tumor lineages. Compound S4 was the most active against Raji, a lymphoma lineage, promoting cell death with characteristics that including membrane permeabilization, dissipation of the mitochondrial potential, increased superoxide production, and lysosomal membrane permeabilization. The use of cell death inhibitors such as Z-VAD-FMK (caspase inhibitor), necrostatin-1 (receptor-interacting serine/threonine-protein kinase 1 inhibitor), E-64 (cysteine peptidases inhibitor), and N-acetyl- L-cysteine (antioxidant) did not decrease compound S4-dependent cell death. Additionally, we tested the effect of cellular activity on adherent human tumor cells. The highest reduction of cellular activity was observed in A549 cells, a lung carcinoma lineage. In this lineage, the effect on the reduction of the cellular activity was due to cell cycle arrest, without plasma membrane permeabilization, loss of the mitochondrial potential or lysosomal membrane permeabilization. Compound S4 was able to inhibit cathepsin B and L by a nonlinear competitive (negative co-operativity) and simple-linear competitive inhibitions, respectively. The potency of inhibition was higher against cathepsin L. Compound S4 promoted cell cycle arrest at G (0) and G (2) phase, and increase the expression of p16 and p21 proteins. In conclusion, compound S4 is an interesting molecule against cancer, promoting cell death in the human lymphoma lineage Raji and cell cycle arrest in the human lung carcinoma lineage A549. (AU)

Processo FAPESP: 18/04095-0 - Abordagens analíticas para a descoberta de compostos citotóxicos desconhecidos a partir de plantas
Beneficiário:Thiago André Moura Veiga
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/25112-4 - Avaliação de moduladores da atividade de proteases envolvidas em processos patológicos
Beneficiário:Wagner Alves de Souza Júdice
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/18990-5 - Estudo dos mecanismos celulares e moleculares na morte de células tumorais por peptídeos antimicrobianos
Beneficiário:Edgar Julian Paredes-Gamero
Linha de fomento: Auxílio à Pesquisa - Regular