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

0389633 - BFÚ 2013 RIV DE eng J - Článek v odborném periodiku
Hammerová, J. - Uldrijan, S. - Táborská, E. - Vaculová, Alena - Slaninová, I.
Necroptosis modulated by autophagy is a predominant form of melanoma cell death induced by sanguilutine.
Biological Chemistry. Roč. 393, č. 7 (2012), s. 647-658. ISSN 1431-6730. E-ISSN 1437-4315
Grant ostatní: GA ČR(CZ) GA525/08/0819; GA MŠk(CZ) LC06077; GA MŠk(CZ) LH12176; GA MZd(CZ) NS10236-3/2009
Program: LC; LH
Institucionální podpora: RVO:68081707
Klíčová slova: BCL-2 FAMILY PROTEINS * MITOCHONDRIAL APOPTOSIS * GLUTATHIONE DEPLETION
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 2.683, rok: 2012

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.
Trvalý link: http://hdl.handle.net/11104/0218532