Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation.
Chem Biol Drug Des
; 87(6): 895-904, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26804061
ABSTRACT
DMAKO-05((S)-1-((5E,8E)-5,8-bis(hydroxyimino)-1,4-dimethoxy-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 3-methylbutanoate) is a novel oxime derivative of shikonin, the major component extracted from Chinese herb Lithospermun erythrorhizon. Here, we report that DMAKO-05 had an antitumor activity against mouse melanoma cell line B16F0. Our studies indicated that DMAKO-05 not only inhibited B16F0 proliferation and migration but also led to cell cycle arrest at G1 phase and cell apoptosis, in which DMAKO-05 triggered mitochondrial-mediated apoptosis signal including caspase-9/3 and PARP. In response to DMAKO-05 treatment, the Akt-mediated survival signals were remarkably attenuated in B16F0 cells. Collectively, DMAKO-05 has a strong cytotoxicity in B16F0 cells via inhibiting Akt activation, inducing G1 arrest, and promoting B16F0 cell apoptosis. DMAKO-05 might serve as a potential candidate lead compound for melanoma.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Naftoquinonas
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Proliferação de Células
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Proteínas Proto-Oncogênicas c-akt
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Melanoma
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Antineoplásicos Fitogênicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article