Psammaplin A induces Sirtuin 1-dependent autophagic cell death in doxorubicin-resistant MCF-7/adr human breast cancer cells and xenografts.
Biochim Biophys Acta
; 1850(2): 401-10, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25445714
ABSTRACT
BACKGROUND:
Psammaplin A (PsA) is a natural product isolated from marine sponges, which has been demonstrated to have anticancer activity against several human cancer cell lines via the induction of cell cycle arrest and apoptosis. New drugs that are less toxic and more effective against multidrug-resistant cancers are urgently needed.METHODS:
We tested cell proliferation, cell cycle progression and autophagic cell death pathway in doxorubicin-resistant MCF-7 (MCF-7/adr) human breast cancer cells. The potency of PsA was further determined using an in vivo xenograft model. RESULTS ANDCONCLUSION:
PsA significantly inhibited MCF-7/adr cells proliferation in a concentration-dependent manner, with accumulation of cells in G2/M phase of the cell cycle. PsA significantly decreased SIRT1 enzyme activity and reduced expression of SIRT1 protein in the cultured cells with greater potency than sirtinol or salermide. Acetylation of p53, a putative target of SIRT1, increased significantly following PsA treatment. In addition, PsA markedly increased the expression levels of autophagy-related proteins. In support of this, it was found that PsA significantly increased the expression of damage-regulated autophagy modulator (DRAM), a p53-induced protein. GENERALSIGNIFICANCE:
The results of this study suggest that PsA is sufficient to overcome multidrug-resistant cancer via SIRT1-mediated autophagy in MCF-7/adr breast cancer cells, indicating that PsA has therapeutic potential for clinical use.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Tirosina
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Neoplasias da Mama
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Doxorrubicina
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Resistencia a Medicamentos Antineoplásicos
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Dissulfetos
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Sirtuína 1
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Antibióticos Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article