Dataset Information

Curcumol Targets the VHL/HIF-1α Axis to Suppress Glycolysis-Driven Progression in Colorectal Cancer.

ABSTRACT: Background: Hypoxia-induced glycolysis represents a hallmark of colorectal cancer (CRC) progression and contributes significantly to therapeutic resistance. Curcumol, a natural sesquiterpenoid derived from Curcumae Rhizoma, has demonstrated promising anti-tumor properties. However, its impact on metabolic reprogramming under hypoxic conditions remains largely undefined. Objective: The objective of this study was to elucidate the potential of Curcumol in inhibiting glycolytic reprogramming and impede CRC progression via regulation of the VHL/HIF-1α signaling pathway. Methods: CRC cells and orthotopic mouse models were treated with Curcumol under chemically induced hypoxic conditions. Metabolic alterations were evaluated using Seahorse extracellular flux analysis, Western blot analysis, quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC) and co-immunoprecipitation (Co-IP). Functional validation of glycolysis and epithelial-mesenchymal transition (EMT) phenotypes was conducted through in vitro and in vivo assays. Results: Curcumol inhibited HIF-1α-mediated metabolic reprogramming by upregulating VHL expression, thereby promoting HIF-1α degradation. This effect led to the downregulation of key glycolytic genes (HK2, LDHA, and GLUT1), decreased glycolytic flux, and lactate production, ultimately suppressing CRC cell proliferation and invasion. The anti-tumor efficacy of Curcumol was validated in both in vitro and in vivo models. Moreover, Curcumol effectively reversed the hypoxia-induced epithelial-mesenchymal transition (EMT) phenotype, suggesting that its metabolic regulatory effects may contribute to reduced metastatic potential. Conclusions: Curcumol suppresses glycolysis and CRC progression by activating the VHL/HIF-1α signaling axis. These findings underscore the potential of Curcumol as a natural metabolic regulator capable of reversing tumor metabolic reprogramming, offering a promising therapeutic strategy for CRC treatment.

SUBMITTER: Wang G

PROVIDER: S-EPMC12468461 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Curcumol Targets the VHL/HIF-1α Axis to Suppress Glycolysis-Driven Progression in Colorectal Cancer.

Wang Gang G Yue Zengyaran Z Yin Gang G Zhu Lifeng L Zhou Wen W Sun Ruiqian R Bi Tingting T Zhao Lin L Bian Yong Y Tang Decai D

Cancers 20250914 18

<b>Background</b>: Hypoxia-induced glycolysis represents a hallmark of colorectal cancer (CRC) progression and contributes significantly to therapeutic resistance. Curcumol, a natural sesquiterpenoid derived from Curcumae Rhizoma, has demonstrated promising anti-tumor properties. However, its impact on metabolic reprogramming under hypoxic conditions remains largely undefined. <b>Objective</b>: The objective of this study was to elucidate the potential of Curcumol in inhibiting glycolytic reprog ...[more]

PMID: 41008845

Similar Datasets

Project description:The pathogenesis of neuropathic pain is complex, and effective treatment methods are lacking in clinical practice. Recent studies have shown that glucose metabolism reprogramming may be involved in the process of neuropathic pain, but its role and molecular regulatory mechanisms in neuropathic pain are still unclear. In this study, a rat model of chronic constriction injury of the sciatic nerve (CCI) was established, and the pain threshold was evaluated through behavioural analysis. Morphological staining, transmission electron microscopy, transcriptome sequencing, Western blotting, immunofluorescence staining, ELISA, and the whole-cell patch clamp technique were used to systematically observe neuropathological changes, identify differentially expressed genes and associated pathways, and measure the expression levels of glycolysis-related indicators and the key regulatory factor fibroblast growth factor 4 (FGF4). The results showed that the pain threshold of rats decreased and that the structure of sciatic nerve tissue was damaged after CCI. Transcriptome sequencing of the sciatic nerve showed a significant increase in the expression levels of glycolysis-related indicators. Subsequent experiments confirmed that FGF4 expression was downregulated in the sciatic nerve and spinal dorsal horn after CCI, whereas the expression of hypoxia-inducible factor-1α (HIF-1α) and its key downstream glycolytic enzymes was upregulated, accompanied by increased levels of lactic acid and proinflammatory cytokines and decreased ATP levels. The spinal dorsal horn exhibited both synaptic structural abnormalities and neuronal hyperexcitability. Inhibiting HIF-1α alleviated pain and suppressed glycolysis, whereas the overexpression of FGF4 specifically reversed the increase in HIF-1α expression, inhibited neuronal glycolysis, and reduced neuroinflammation and central sensitization, ultimately effectively relieving pain. This study reveals the core role of the FGF4/HIF-1α-mediated regulation of neuronal glycolysis in neuropathic pain, providing a new theoretical basis and experimental evidence for a deeper understanding of the metabolic mechanism of neuropathic pain and the development of targeted treatment strategies.

Dataset Information

Curcumol Targets the VHL/HIF-1α Axis to Suppress Glycolysis-Driven Progression in Colorectal Cancer.

Publications

Curcumol Targets the VHL/HIF-1α Axis to Suppress Glycolysis-Driven Progression in Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets