The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells.
Apoptosis
; 16(9): 924-39, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21667044
ABSTRACT
Naphthazarin (DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is a naturally available 1,4-naphthoquinone derivatives. In this study, we focused on elucidating the cytotoxic mechanism of naphthazarin in A549 non-small cell lung carcinoma cells. Naphthazarin reduced the A549 cell viability considerably with an IC(50) of 16.4 ± 1.6 µM. Naphthazarin induced cell death in a dose- and time-dependent manner by activating apoptosis and autophagy pathways. Specifically, we found naphthazarin inhibited the PI3K/Akt cell survival signalling pathway, measured by p53 and caspase-3 activation, and PARP cleavage. It also resulted in an increase in the ratio of Bax/Bcl2 protein levels, indicating activation of the mitochondrial apoptotic pathway. Similarly naphthazarin triggered LC3II expression and induced autophagic flux in A549 cells. We demonstrated further that naphthazarin is a microtubule inhibitor in cell-free system and in A549 cells. Naphthazarin treatment depolymerized interphase microtubules and disorganised spindle microtubules and the majority of cells arrested at the G(2)/M transition. Together, these data suggest that naphthazarin, a microtubule depolymerizer which activates dual cell death machineries, could be a potential novel chemotherapeutic agent.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Naftoquinonas
/
Apoptose
/
Microtúbulos
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article