Accessible Requires Authentication Published by De Gruyter July 1, 2012

Necroptosis modulated by autophagy is a predominant form of melanoma cell death induced by sanguilutine

Jindřiška Hammerová, Stjepan Uldrijan, Eva Táborská, Alena Hyršlová Vaculová and Iva Slaninová
From the journal Biological Chemistry

Abstract

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.


Corresponding author

Received: 2011-11-30
Accepted: 2012-4-7
Published Online: 2012-07-01
Published in Print: 2012-07-01

©2012 by Walter de Gruyter Berlin Boston