Iridoids from Valeriana jatamansi induce autophagy-associated cell death via the PDK1/Akt/mTOR pathway in HCT116 human colorectal carcinoma cells.
Bioorg Chem
; 87: 136-141, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30884307
ABSTRACT
Chlorovaltrates U-W (1-3), three previously undescribed iridoids, together with four known analogues were isolated from the roots of Valeriana jatamansi. Their structures were elucidated by means of spectroscopic analyses (HRESIMS, NMR). The cytotoxicity of all isolates was evaluated. Compounds 5-7 exhibited selective cytotoxicity against HCT116 cells, with IC50 values of 9.3, 1.7 and 2.2⯵M, respectively. The preliminary mechanistic study revealed that, the cytotoxicity effect of 6 was attributed to Akt/mTOR activation blockade via inhibition of PDK1 phosphorylation. Meanwhile, compound 6 could induce autophagosome formation in HCT116 cells via suppressing its downstream Akt/mTOR. These findings show that compound 6 could be of great importance to the development of anti-colon cancer agents.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Valeriana
/
Iridoides
/
Inibidores de Proteínas Quinases
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article