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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 7
Document type: Journal article
Source: Journal of Cellular Biochemistry; v. 120, n. 6, p. 9608-9623, JUN 2019.
Web of Science Citations: 1
Abstract

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)

FAPESP's process: 18/04095-0 - Analytical Approaches for Discovering Unknown Cytotoxic Compounds from Plants
Grantee:Thiago André Moura Veiga
Support type: Regular Research Grants
FAPESP's process: 16/25112-4 - Evaluation of modulators of the activity of proteases involved in pathological processes
Grantee:Wagner Alves de Souza Júdice
Support type: Regular Research Grants
FAPESP's process: 16/18990-5 - Studies of cellular and molecular mechanisms of tumor cell death induced by antimicrobial peptides
Grantee:Edgar Julian Paredes-Gamero
Support type: Regular Research Grants