Evidence map›Paper›PMID 38804345›Full record

ArticleCurrent cancer drug targets2024

Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis.

Xiangyang Zhou, Di Wu, Linmiao Zhu, Ruohan Li, Haitao Yu, Wenjuan Li

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Article in Current cancer drug targets, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xiangyang ZhouCollege of Basic Medicine, Hebei University, Baoding, Hebei, 071000, China.
Di WuCollege of Basic Medicine, Hebei University, Baoding, Hebei, 071000, China.
Linmiao ZhuCollege of Basic Medicine, Hebei University, Baoding, Hebei, 071000, China.
Ruohan LiCollege of Basic Medicine, Hebei University, Baoding, Hebei, 071000, China.
Haitao YuDepartment of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, China.
Wenjuan LiCollege of Basic Medicine, Hebei University, Baoding, Hebei, 071000, China.

Funding

Hebei Provincial Natural Science Foundation of China C2023201073Medical Science Foundation of Hebei University 2021A01Projects of Basic Scientific Research of Heilongjiang Education Department 2017-QYKYYWF-0754
6 · The paper itself

Abstract

backgroundThe energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from

methodsDifferential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways.

resultsWe first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia.

conclusionTaken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.

Indexed as

GlycolysisHypoxia-Inducible Factor 1, alpha SubunitIsocitrate DehydrogenaseLiver NeoplasmsSignal TransductionTumor Suppressor Protein p53WithanolidesCarcinogenesisCell ProliferationGene Expression Regulation, NeoplasticHep G2 CellsHumansHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIDH1 protein, humanIsocitrate DehydrogenaseTP53 protein, humanTumor Suppressor Protein p53withaferin AWithanolidesaerobic glycolysisHIF-1α.isocitrate dehydrogenase 1liver cancerp53Withaferin A

Identifiers

PMID38804345

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