Chromen based Novel Molecule from Wadelia trilobata Exhibits Molecular Impediment on the Proliferation of Chronic Myeloid Leukemia by Inducing Apoptosis Linked Suppression of STAT5/Bcl-XL Signal Pathway

Authors : Uday Venkatesh; Sreerohini Sagi; Satish Kumar Murari; Farhan Zameer

Volume/Issue : Volume 8 - 2023, Issue 8 - August

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Chronic myeloid leukemia (CML) being the first disease identified with the association of chromosomal abnormality referred as Philadelphia condition is also the most widely studied disease among human malignancy. In this study, we characterized the the molecular hindrance property of the novel molecule MPC [7 methoxy 3(4 methoxy 2 methylphenyl) 5 methyl 4H chromen 4 one], extracted from Wadelia trilobata against the actively proliferating CML cells. Nuclear staining and flowcytometry analysis revealed the apoptotic activity of MPC. Further studies through immunobloting and real-time PCR, shows down regulation of anti-apoptosis inducing proteins of Bcl2 family specific to CML cells. Molecular docking also displayed that the MPC molecule inhibits JAK-STAT5 pathway where BclXL is activated transcriptionally through STAT5 for initiating anti-apoptosis and shutdowns the RAS mediated BclXL assisted anti- apoptotic pathway. In brief this chromen based MPC molecule effectively suppress the proliferation of chronic myeloid leukemia by inducing apoptosis and the molecule promises the effective drug alternate to tyrosine kinase inhibitor (TKI) for treating CML.

Keywords : CML; Philadelphia Chromosomes; BclXL Protein ; Apoptosis ; BCR-ABL Protein ; Tyrosine Kinase.


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31 - December - 2023

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