Novel indolyl-chalcones target stathmin to induce cancer cell death.
Cell Cycle
; 15(9): 1288-94, 2016 05 02.
Article
em En
| MEDLINE
| ID: mdl-26986925
ABSTRACT
Efficacy of current therapies for advanced and metastatic cancers remains a challenge in clinical practice. We investigated the anti-cancer potency of 3 novel indoly-chalcones (CITs). Our results indicated the lead molecule CIT-026 (Formula = C20H16FNO) induced cell death in prostate and lung cancer cell lines at sub-micromolar concentration. CITs (CIT-026, CIT-214, CIT-223) lead to microtubule destabilization, cell death and low cell proliferation, which in part was dependent on stathmin (STMN1) expression. Knockdown of STMN1 with siRNA against STMN1 in part restored viability of cancer cells in response to CITs. Further, CIT-026 and CIT-223 blocked cancer cell invasion through matrigel-coated chambers. Mechanistically, CITs inhibited phosphorylation of STMN1 leading to STMN1 accumulation and mitotic catastrophe. In summary, we have synthetized novel anti-cancer CIT molecules and defined their mechanism of action in vitro.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Chalconas
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Estatmina
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Terapia de Alvo Molecular
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Indóis
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article