Combining in silico and in vitro approaches for understanding the mechanism of action of the galactomannan extracted from Cassia grandis seeds against colorectal cancer.

Autor: Albuquerque PBS; Programa de Pós-Graduação em Saúde e Desenvolvimento Socioambiental - Universidade de Pernambuco, Garanhuns, PE, Brasil; Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada - UPE Santo Amaro, Brasil; Laboratório de Bioprospecção e Etnofarmacotoxicologia Aplicada (LABEA) - Universidade de Pernambuco, Garanhuns, PE, Brasil. Electronic address: priscilla.albuquerque@upe.br., Ramos LFS; Programa de Pós-Graduação em Saúde e Desenvolvimento Socioambiental - Universidade de Pernambuco, Garanhuns, PE, Brasil., Dantas MIJDS; Programa de Pós-Graduação em Saúde e Desenvolvimento Socioambiental - Universidade de Pernambuco, Garanhuns, PE, Brasil., Othmar FS; Laboratório de Bioprospecção e Etnofarmacotoxicologia Aplicada (LABEA) - Universidade de Pernambuco, Garanhuns, PE, Brasil., Galúcio JM; Instituto de Biodiversidade e Florestas - Universidade Federal do Oeste do Pará, Brasil., Costa KSD; Instituto de Biodiversidade e Florestas - Universidade Federal do Oeste do Pará, Brasil., Costa MJF; Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada - UPE Santo Amaro, Brasil; Laboratório Multiusuário de Biotecnologia do Sertão Pernambucano (BIOSPE) - Universidade de Pernambuco, Arcoverde, PE, Brasil., Rodrigues NER; Laboratório de Bioprospecção e Etnofarmacotoxicologia Aplicada (LABEA) - Universidade de Pernambuco, Garanhuns, PE, Brasil., Lima LRA; Programa de Pós-Graduação em Saúde e Desenvolvimento Socioambiental - Universidade de Pernambuco, Garanhuns, PE, Brasil., Sette-de-Souza PH; Programa de Pós-Graduação em Saúde e Desenvolvimento Socioambiental - Universidade de Pernambuco, Garanhuns, PE, Brasil; Laboratório Multiusuário de Biotecnologia do Sertão Pernambucano (BIOSPE) - Universidade de Pernambuco, Arcoverde, PE, Brasil.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2025 Jan; Vol. 284 (Pt 1), pp. 137909. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1016/j.ijbiomac.2024.137909
Abstrakt: This study aimed to investigate the antitumor activity of galactomannan extracted from Cassia grandis seeds (GCg) against colorectal cancer cells using both experimental and computational approaches. Galactomannan was extracted from C. grandis seeds and prepared into solutions with varying concentrations. The cytotoxicity of these solutions was tested on HT-29 and HCT-116 colorectal cancer cell lines using the MTT assay. Additionally, computational evaluations, including molecular docking and molecular dynamics simulations, were performed to explore the potential binding interactions of GCg with cyclin-dependent kinase 2 (CDK2). The experimental results demonstrated that GCg significantly inhibited the proliferation of HT-29 cells, especially at concentrations of 5 mg/mL. On the other hand, no concentration inhibited >30 % of HCT-116 cells. Computational analysis revealed that GCg could bind to the ATP-binding site of CDK2, promoting the inactive DFG-out conformation, similar to the known inhibitor K03861. This interaction suggests a mechanism through which GCg may exert its anticancer effects. GCg exhibits significant cytotoxic activity against HT-29 colorectal adenocarcinoma cells, likely through the inhibition of CDK2; however, its efficacy against HCT-116 cells is limited, possibly due to structural differences in the molecular targets. To the best of the authors' knowledge, no studies have explored the applications of GCg in cancers, particularly colorectal ones. Further studies are needed to explore the antimetastatic effects and potential clinical applications of GCg in colorectal cancer treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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