Posted on Jul 15, 2018, 10 p.m.
X-ray crystallography and kinase-inhibitor specificity profiling has revealed that curcumin binds to the kinase enzyme dual specificity tyrosine regulated kinase at the atomic level, an interaction that impairs cell proliferation and reduces cancer burden, as published in the Proceedings of the National Academy of Sciences.
Researchers from the University of California in collaboration with Peking University and Zhejiang University discovered the previously unreported co-crystal structure of curcumin to bind to protein kinase target biochemical interaction of the naturally occurring turmeric compound binding to and inhibiting DYRK2 leading to impediment of proteasome; who also note that curcurmin alone may not be the answer as it is expelled from the body quickly, to be an effective drug it needs to be modified to enter the bloodstream and stay long enough to target cancer.
Kinases IKK and GSK3 enzymes were thought to be curcumin targets leading to anticancer effects, but the co-crystal structure of curcumin with DYRK2 along with an 140 panel kinase inhibitor profiling has revealed curcumin binds strongly to active sites of DYRK2 inhibiting it 500 times more potently than GSK3 or IKK, showing anticancer potential for chemo-sensitive and proteasome inhibitor resistant and adapted cancers.
Depletion of DYRK2 impairs proteasome activity and inhibits cancer proliferation rates to significantly reduce tumor burden in model mice. Used in combination with FDA approved multiple myeloma drug carfilzomib it induced increased rates of cancer cell death with normal noncancerous cells being less affected. Researchers suggest although further work is needed but their results show targeting proteasome regulators in combination with inhibitors could be used as cancer therapy with less side effects.
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