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Sphingosine analogue FTY720 sensitizes arsenic trioxide-induced autophagic cell death in human malignant glioma cells

Siraj Pallichankandy, Anees Rahman, Faisal Thayyullathil, Sehamuddin Galadari
Published in : HAMDAN MEDICAL JOURNAL ; Vol 10, No 1 (2017)
DOI : 10.7707/hmj.607

Abstract


Malignant gliomas are known to be resistant to therapies that induce apoptosis. Recently, several lines of evidence indicate that glioblastoma cells may be less resistant to therapies that induce autophagy. Therefore, drugs targeting autophagy are considered as promising in the management of malignant gliomas. The purpose of this study was to investigate the antitumour potential of FTY720, a novel sphingosine analogue, and to elucidate the molecular mechanism of its cytotoxic effects on malignant glioma cells. We demonstrate that FTY720 induces autophagy but not apoptosis in malignant glioma cells. We found that FTY720 sensitizes arsenic trioxide-induced autophagic cell death in glioma cells and that FTY720arsenic trioxide (ATO) combined treatment induces autophagy through the inhibition of the Akt/mTOR signalling pathway. Our findings provide a possible base for combinatorial therapeutic application of FTY720ATO in the management of malignant gliomas.



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