Abstract:
Gramicidin A is a well-known antibiotic and recently was reported to induced tumour
cell death, however, little is understood about the molecular mechanism of gramicidin
A as a therapeutic agent for solid tumours. Similarly, its role in liquid cancer is
unknown.Here, we investigated the role of gramicidin A in leukemic cells. Leukemia
is the cancer of white blood cells and is of two origin i-e myeloid and lymphoid origin.
Gramicidin A upon testing in vitro interferes with the proliferation potential of
PML/RARα-positive APL cells and BCR-ABL positive CML cells. The current study
evaluated the cell cytotoxicity of gramicidin A and its anti proliferative activity on
NB4 and K562 cell lines. Generalized toxicity is a significant challenge to the
development of ionophores as therapies for human cancer. But we identified a
concentration of Gramicidin A showing no hemolysis. Furthermore, we investigated
the combine effect of already approved treatments of CML and APL with Gramicidin
A and is has shown additive effect in both cases. Similarly, the expression analysis
indicated that Gramicidin A interferes with the β-catenin dependent leukemogenesis
and downregulates AXL-RTK in APL cells with the expected downregulation of
downstream c-Myc, Eya3 and Axin 2 related to the Wnt/β-catenin signalling. Taken
together, these results demonstrate a new role for gramicidin A as a potent inhibitor
in case of myeloid leukemia.
