Necroptosis modulated by autophagy is a predominant form of melanoma cell death induced by sanguilutine
| Autoři | |
|---|---|
| Rok publikování | 2012 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Biological Chemistry |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1515/hsz-2011-0279 |
| Obor | Biochemie |
| Klíčová slova | apoptosis; Bcl-2; benzophenanthridine alkaloids; LC3; necrostatin-1; RIP1 |
| Přiložené soubory | |
| Popis | 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. |
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