Authors :
Uday Venkatesh; Sreerohini Sagi; Satish Kumar Murari; Farhan Zameer
Volume/Issue :
Volume 8 - 2023, Issue 8 - August
Google Scholar :
https://bit.ly/3TmGbDi
Scribd :
https://tinyurl.com/mrxufvn7
DOI :
https://doi.org/10.5281/zenodo.8297657
Abstract :
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.
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.
