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Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model

Title
Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model
Authors
Choi, JinaShin, Phil-KyungKim, YuriHong, Chang PyoChoi, Sang-Woon
Ewha Authors
김유리
SCOPUS Author ID
김유리scopus
Issue Date
2019
Journal Title
EUROPEAN JOURNAL OF NUTRITION
ISSN
1436-6207JCR Link

1436-6215JCR Link
Citation
EUROPEAN JOURNAL OF NUTRITION vol. 58, no. 4, pp. 1635 - 1645
Keywords
Colon cancer stem cellGlycolysisMetabolic reprogrammingMitochondriaWalnut
Publisher
SPRINGER HEIDELBERG
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
PurposeWalnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism.MethodsCD133(+)CD44(+) HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 mu g/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests.ResultsRNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ECAR=36.98 mpH/min/ptn, p=0.02) and oxidative pathway (OCR=29.18pmol/min/ptn, p=0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (OCR=111.5pmol/min/ptn, p=0.0006). WPE treatment also increased glucose uptake (=0.39pmol/mu L, p=0.002) and lactate production (=0.08nmol/mu L, p=0.005).ConclusionsWPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.
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DOI
10.1007/s00394-018-1708-z
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신산업융합대학 > 식품영양학과 > Journal papers
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