The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells
Identifieur interne : 001497 ( Main/Exploration ); précédent : 001496; suivant : 001498The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells
Auteurs : Bipul R. Acharya [Inde, États-Unis] ; Surela Bhattacharyya [Inde] ; Diptiman Choudhury [Inde] ; Gopal Chakrabarti [Inde]Source :
- Apoptosis [ 1360-8185 ] ; 2011-09-01.
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Abstract
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 IC50 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 G2/M transition. Together, these data suggest that naphthazarin, a microtubule depolymerizer which activates dual cell death machineries, could be a potential novel chemotherapeutic agent.
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DOI: 10.1007/s10495-011-0613-1
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