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

Abstract:

BACKGROUND:Cytolysins are pore-forming toxins that show anticancer activity by a mechanism hitherto poorly investigated. MATERIALS AND METHODS: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). RESULTS: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. CONCLUSION:Cytolysins were shown to be toxic to glioblastoma cells by activating several intracellular signaling pathways and resulting in necrosis-like cell death.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Soletti RC,Alves T,Vernal J,Terenzi H,Anderluh G,Borges HL,Gabilan NH,Moura-Neto V

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

1209-15

issue

4

eissn

0250-7005

issn

1791-7530

pii

30/4/1209

journal_volume

30

pub_type

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