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International Journal of Applied Science - Research and Review
ISSN 2394-9988
E u r o p e a n C o n f e r e n c e o n
Agriculture, Horticulture
& Epigenetics
F e b r u a r y 2 5 - 2 6 , 2 0 1 9
P a r i s , F r a n c e
Agriculture & Epigenetics 2019
Targeting MYC remains a major therapeutic goal in cancer chemotherapy.
Here, we identified that proscillaridin, a cardiac glycoside approved for
heart failure treatment, targets specifically leukemic cells overexpressing MYC
at clinically relevant doses. Proscillaridin induced rapid downregulation of MYC
proteins, reduced proliferation in leukemic cell lines and in leukemic stem cell
populations. Transcriptomic profile of leukemic cells after treatment showed
a downregulation of gene sets involved in cell replication, MYC pathways
and an upregulation of genes involved in hematopoietic differentiation.
Interestingly, low dose of proscillaridin treatment induced a significant loss
of lysine acetylation on histone H3 at lysine 9, 14, 18 and 27. Acetylome
profiling uncovered that acetylation loss included also non-histone proteins
such as MYC itself, MYC target proteins, and a series of histone acetylation
regulators. Loss of acetylation resulted from the rapid downregulation of
histone acetyltransferase proteins after treatment. Overall, these results
strongly support the re-purposing of proscillaridin in MYC overexpressing
leukemia and suggest a novel strategy to target indirectly MYC by inducing
the downregulation of a series of histone acetyltransferases involved in its
stability.
Biography
Noël J-M Raynal has completed his PhD from University of
Québec and Postdoctoral studies from MD Anderson Cancer
Center and Temple University. He is the Director of an academic
laboratory at the Centre de recherche of CHU-Sainte-Justine in
Montreal affiliated with the Department of pharmacology and
physiology of the Université de Montréal. His research focuses
on epigenetic therapy of pediatric cancers.
Targeting MYC overexpressing leukemia with cardiac
glycoside proscillaridin through downregulation of histone
acetyltransferases
Noël J-M Raynal
Université de Montréal, Canada
Noël J-M Raynal, Int J Appl Sci Res Rev 2019, Volume: 6
DOI: 10.21767/2394-9988-C1-008