Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells.

Oncotarget
Parthasarathy RangarajanAnimesh Dhar

Abstract

Pancreatic cancer is the fourth leading cause of cancer deaths in the US and no significant treatment is currently available. Here, we describe the effect of crocetinic acid, which we purified from commercial saffron compound crocetin using high performance liquid chromatography. Crocetinic acid inhibits proliferation of pancreatic cancer cell lines in a dose- and time-dependent manner. In addition, it induced apoptosis. Moreover, the compound significantly inhibited epidermal growth factor receptor and Akt phosphorylation. Furthermore, crocetinic acid decreased the number and size of the pancospheres in a dose-dependent manner, and suppressed the expression of the marker protein DCLK-1 (Doublecortin Calcium/Calmodulin-Dependent Kinase-1) suggesting that crocetinic acid targets cancer stem cells (CSC). To understand the mechanism of CSC inhibition, the signaling pathways affected by purified crocetinic acid were dissected. Sonic hedgehog (Shh) upon binding to its cognate receptor patched, allows smoothened to accumulate and activate Gli transcription factor. Crocetinic acid inhibited the expression of both Shh and smoothened. Finally, these data were confirmed in vivo where the compound at a dose of 0.5 mg/Kg bw suppressed grow...Continue Reading

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Citations

Sep 12, 2018·Journal of Cellular Biochemistry·Maliheh MoradzadehHamid Reza Sadeghnia
Jan 2, 2019·Anti-cancer Agents in Medicinal Chemistry·Alessandro ColapietroClaudio Festuccia
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Methods Mentioned

BETA
xenografts
Flow
Fluorescence microscopy
flow cytometry
xenograft
NMR
light microscopy

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