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

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.