Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.
Bioorg Med Chem Lett
; 31: 127673, 2021 01 01.
Article
em En
| MEDLINE
| ID: mdl-33161122
ABSTRACT
Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
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Apoptose
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Caspase 3
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Inibidores de Poli(ADP-Ribose) Polimerases
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Poli(ADP-Ribose) Polimerase-1
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Fabaceae
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2021
Tipo de documento:
Article