Autophagic flux modulation by Wnt/β-catenin pathway inhibition in hepatocellular carcinoma

PloS One
Lilia TurciosRoberto Gedaly

Abstract

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, mediated in part by the simultaneous disruption of mitochondrial respiration and glycolysis. We demonstrated that FH535 decreased HCC tumor progression in a mouse xenograft model. For the first time, we showed the inhibitory effect of an FH535 derivative, FH535-N, alone and in combination with sorafenib on HCC cell proliferation. Our study revealed the contributing effect of Wnt/β-catenin pathway inhibition by FH535 and its derivative (FH535-N) through disruption of the autophagic f...Continue Reading

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Citations

Jul 2, 2019·Journal of Extracellular Vesicles·Ye ZengBingmei M Fu
Nov 25, 2020·Geriatrics & Gerontology International·Takahiro Kamihara, Toyoaki Murohara
Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Apr 25, 2021·Molecular Biology Reports·Magdelyn Mei-Theng WongSin-Yeang Teow
Apr 29, 2021·Neuropsychiatric Disease and Treatment·Ruijie GengXiao Huang
Mar 31, 2021·Molecular Metabolism·Riya ShresthaFrances L Byrne
Jun 3, 2021·Cancers·Iram FatimaVishal Chandra
May 28, 2021·Frontiers in Oncology·Marike W van GisbergenLudwig J Dubois

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Methods Mentioned

BETA
xenograft
Protein Assay
PCR
Flow Cytometry
transfection
Assay

Software Mentioned

ID
GraphPad
Cyto
CytoID
FlowJo
ImageJ
Excel
Wave
Prism

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