In:
bchm, Walter de Gruyter GmbH, Vol. 393, No. 7 ( 2012-07-01), p. 647-658
Kurzfassung:
We show that the plant quaternary benzo[ c ]phenanthridine alkaloid sanguilutine (SL) is a strong inducer of caspase-independent non-apoptotic death in human melanoma cells. Necrostatin-1, a specific inhibitor of necroptosis, completely reversed the cytotoxic effect of SL, suggesting that necroptosis was a predominant type of cell death induced by SL in these cells. In addition, we showed that SL can trigger an autophagic response, as confirmed by GFP-LC3 puncta formation and LC3-II accumulation. Interestingly, we observed a significant decrease in the viability of melanoma cells treated with combination of autophagy inhibitors (3-methyladenine, bafilomycin-A1 and LY294002) and SL. Our results further indicated that autophagy may serve as a pro-survival mechanism, delaying the induction of necroptosis in melanoma cells. The ability of SL to induce caspase-independent non-apoptotic cell death (necroptosis) suggests its possible therapeutic potential in the treatment of apoptosis-resistant melanoma tumours. Furthermore, SL might serve as a useful tool for studying the mechanisms of necroptosis and autophagy induction and the interplay between these two processes.
Materialart:
Online-Ressource
ISSN:
1437-4315
,
1431-6730
DOI:
10.1515/hsz-2011-0279
Sprache:
Englisch
Verlag:
Walter de Gruyter GmbH
Publikationsdatum:
2012
ZDB Id:
1466062-3
SSG:
12
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