Article

Inhibition of MAPK/ERK, PKC and CaMKII signaling blocks cytolysin-induced human glioma cell death.

Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Anticancer research (impact factor: 1.73). 04/2010; 30(4):1209-15. pp.1209-15
Source: PubMed

ABSTRACT Cytolysins are pore-forming toxins that show anticancer activity by a mechanism hitherto poorly investigated.
To investigate how cytolysins are cytotoxic to resistant cancer cells, proliferation and cell death were evaluated on U87 glioblastoma cells treated with toxin Bc2 or equinatoxin-II (EqTx-II).
Toxins Bc2 and EqTx-II decreased cell viability and increased lactate dehydrogenase (LDH) release in a concentration-dependent manner. Swollen, dead or dying cells were negative for TUNEL staining. The pre-treatment with inhibitors of mitogen-activated/extracellular regulated kinase (MEK1), protein kinase C (PKC) or Ca(2+)/calmodulin-dependent kinase II (CaMKII) blocked the toxic effects of toxin Bc2 and EqTx-II, suggesting that calcium entry, activation of MEK1, PKC and CaMKII pathways are involved in the cytotoxicity induced by these cytolysins.
Cytolysins were shown to be toxic to glioblastoma cells by activating several intracellular signaling pathways and resulting in necrosis-like cell death.

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    Article: Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens ε-toxin.
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    PLoS ONE 01/2011; 6(3):e17787. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Ca(2+)/calmodulin-dependent kinase II
 
CaMKII pathways
 
cell death
 
cell viability
 
concentration-dependent manner
 
Cytolysins
 
cytotoxicity induced
 
glioblastoma cells
 
intracellular signaling pathways
 
lactate dehydrogenase
 
mitogen-activated/extracellular
 
necrosis-like cell death
 
protein kinase C
 
resistant cancer cells
 
show anticancer activity
 
toxic effects
 
toxin Bc2
 
Toxins Bc2
 
TUNEL staining
 
U87 glioblastoma cells