J 2012

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

HAMMEROVÁ, Jindřiška, Stjepan ULDRIJAN, Eva TÁBORSKÁ, Alena HYRŠLOVÁ VACULOVÁ, Iva SLANINOVÁ et. al.

Basic information

Original name

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

Authors

HAMMEROVÁ, Jindřiška (203 Czech Republic, guarantor, belonging to the institution), Stjepan ULDRIJAN (203 Czech Republic, belonging to the institution), Eva TÁBORSKÁ (203 Czech Republic, belonging to the institution), Alena HYRŠLOVÁ VACULOVÁ (203 Czech Republic) and Iva SLANINOVÁ (203 Czech Republic, belonging to the institution)

Edition

Biological Chemistry, Berlin, DE, Walter de Gruyter&CO, 2012, 1431-6730

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.683

RIV identification code

RIV/00216224:14110/12:00057556

Organization unit

Faculty of Medicine

UT WoS

000307087600011

Keywords in English

apoptosis; Bcl-2; benzophenanthridine alkaloids; LC3; necrostatin-1; RIP1

Tags

International impact
Změněno: 4/9/2012 14:01, Mgr. Michal Petr

Abstract

V originále

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.

Links

GA525/08/0819, research and development project
Name: Rostlinné zdroje minoritních benzofenanthridinových alkaloidů a studium interakcí těchto alkaloidů s DNA
Investor: Czech Science Foundation, Plant sources of minor benzofenantridine alkaloids and study of heir interaction with DNA
LC06077, research and development project
Name: Centrum chemické genetiky
Investor: Ministry of Education, Youth and Sports of the CR
LH12176, research and development project
Name: Benzofenanthridinové alkaloidy - studium účinků na celulární a molekulární úrovni (Acronym: KBF)
Investor: Ministry of Education, Youth and Sports of the CR
NS10236, research and development project
Name: Terapeutický potenciál inhibice vybraných signálních drah v buňkách maligního melanomu
Investor: Ministry of Health of the CR

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