Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis

Scientific Reports
Ling ChenYan Qiu

Abstract

Inhibition of stearoyl-CoA desaturase 1 (SCD1) has been found to effectively suppress tumor cell proliferation and induce apoptosis in numerous neoplastic lesions. However, mechanism underlying SCD1-mediated anti-tumor effect has maintained unclear. Herein, we reported endo-lipid messenger ceramides played a critical role in tumor fate modulated by SCD1 inhibition. In vitro study in colorectal cancer cells demonstrated inhibition of SCD1 activity promoted apoptosis attributed to mitochondria dysfunctions, upregulation of reaction oxygen species (ROS), alteration of mitochondrial transmembrane potential and translocation of mitochondrial protein cytochrome C. While these effects were mediated by intracellular ceramide signals through induction of ceramide biosynthesis, rather than exclusive SFA accumulation. In vivo study in xenograft colorectal cancer mice showed pharmacologic administration of SCD1 inhibitor A939 significantly delayed tumor growth, which was reversed by L-cycloserine, an inhibitor of ceramide biosynthesis. These results depicted the cross-talk of SCD1-mediated lipid pathway and endo-ceramide biosynthesis pathway, indicating roles of ceramide signals in SCD1-mediated anti-tumor property.

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Citations

Jun 26, 2017·Journal of Hepatology·Mark Kin Fai MaTerence Kin Wah Lee
Feb 26, 2020·The Journal of Experimental Medicine·Jeroen F J BogieJerome J A Hendriks
May 21, 2019·NMR in Biomedicine·Sean Philip ArlauckasEdward James Delikatny
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Feb 23, 2021·Cancer Biology & Therapy·Rui-He ZhengJie Ren
Feb 14, 2018·Biochemical and Biophysical Research Communications·Meenu MaanAndrew D Patterson
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Jul 21, 2021·Nutrition and Cancer·Eric Francisco Contreras-LópezRosa María Oliart-Ros
Dec 26, 2018·Analytical Chemistry·Mei Sun, Zhibo Yang

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Methods Mentioned

BETA
PCR
transfection
xenograft
Assay

Software Mentioned

Quantity One
GraphPad Prism

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