In this paper, we provide evidence that (1) MAs have antileukemic activity, either in vitro or in vivo, in both AML and ALL, alone or in combination with chemotherapeutic drugs, (2) these effects depend on a complex modulation of both autophagy and intracellular signaling pathways regulating cell survival and apoptosis, and (3) are mediated by hERG1 channels. Compared with hERG1 blockers, MAs have a low risk of inducing torsade-de-points cardiac arrhythmias.We thus propose to include these compounds in treatment schedules of resistant acute leukemias in combination with chemotherapeutic drugs.
Macrolide antibiotics exert antileukemic effects by modulating the autophagic flux through inhibition of hERG1 potassium channels / Pillozzi, S.; Masselli, M.; Gasparoli, L.; D'Amico, M.; Polletta, L.; Veltroni, M.; Favre, C.; Basso, G.; Becchetti, A.; Arcangeli, A.. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - ELETTRONICO. - 6:(2016), pp. e423-e427. [10.1038/bcj.2016.32]
Macrolide antibiotics exert antileukemic effects by modulating the autophagic flux through inhibition of hERG1 potassium channels
PILLOZZI, SERENA;MASSELLI, MARIKA;GASPAROLI, LUCA;D'AMICO, MASSIMO;POLLETTA, LUCIA;VELTRONI, MARINELLA;ARCANGELI, ANNAROSA
2016
Abstract
In this paper, we provide evidence that (1) MAs have antileukemic activity, either in vitro or in vivo, in both AML and ALL, alone or in combination with chemotherapeutic drugs, (2) these effects depend on a complex modulation of both autophagy and intracellular signaling pathways regulating cell survival and apoptosis, and (3) are mediated by hERG1 channels. Compared with hERG1 blockers, MAs have a low risk of inducing torsade-de-points cardiac arrhythmias.We thus propose to include these compounds in treatment schedules of resistant acute leukemias in combination with chemotherapeutic drugs.
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