Pb1837: antibiotics; a possible alternate treatment option for myeloid leukemia

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Leukemia is the cancer of white blood cells (WBCs) from myeloid and lymphoid progenitors, which are involved in blood cells production. Based on the progression, myeloid leukemia may be either acute or chronic. This study was focused on Acute promyelocytic leukemia (APL), a sub type of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Despite the encouraging results of FDA-approved therapies, problem of relapse and adoptive resistance remain the two major clinical challenges in the treatment of leukemia. Gramicidin A, an ionophore and well-known antibiotic, has recently been shown to cause tumor cell death, however its role in leukemia has not been explored. Aims: The aim of this study was to explore the possible anticancer role of Gramicidin A in APL and CML. Methods: We used different in-silico tools, pharmacological and biochemical approaches. Results: we report that Gramicidin A interferes with proliferation potential of APL and CML cell lines (p < 0.05 and (p < 0.0001)). The combined effect of Gramicidin A with imatinib for CML and ATRA for APL showed additive anticancer effect ((p < 0.0001) which was related to AXL-RTK dependent down regulation of β-catenin target genes such as, c-Myc, Eya3, and Axin 2 (p < 0.0001). Further Gramicidin A did not induce any hemolysis of red blood cells which shows its safety with no toxicity. Summary/Conclusion: Our results suggest that gramicidin A strongly interfere with leukemogenic potential of APL and CML without any toxicity and can be a possible alternative candidate for therapeutic interventions in future. Keywords: Leukemia