Costunolide reduces glycolysis-associated activation of hepatic stellate cells via inhibition of hexokinase-2

Ban, D.; Hua, Shucheng; Zhang, Wen; Shen, Chao; Miao, Xuehua; Liu, Wensheng

doi:10.1186/s11658-019-0179-4

Cited by 23 publications

(17 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HK2, known as a pivotal rate-limiting enzyme, mainly regulates cell glycolysis. Targeting HK2 with costunolide decreased the uptake of glucose and lactate accumulation, resulting in suppression of hepatic stellate cell viability, which is the major cell for hepatic fibrosis (37). It has been demonstrated that glycolysis metabolism was associated with tumor cell development and progression in oral tongue squamous cell carcinomas (38).…”

Section: Discussionmentioning

confidence: 99%

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD-L1) regulates tumor cells glycolysis using real time PCR (RT-PCR), western blotting and flow cytometry. PD-L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD-L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis-associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD-L1 high-expressed cell line. Overexpressed PD-L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD-L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD-L1-overexpressed cell line (PD-L1-OV) MOLM-13 exhibited rapid tumor progression. Glycolysis-associated genes were highly expressed in tumor tissues of PD-L1-OV MOLM-13, with increased Ki67. Based on these findings, PD-L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.

show abstract

Section: Discussionmentioning

confidence: 99%

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…According to these findings, inhibitors of Hh signaling, HIF1α, glycolysis and lactate accumulation could be helpful to limit HSC activation and revert aHSCs to a quiescent state. Costunolide, a natural compound with anti-inflammatory, anti-oxidant and anti-tumor actions [57], has been recently shown to negatively modulate HSC activated phenotype, through inhibition of hexokinase 2, a ratelimiting glycolytic enzyme [58], which maintains glucose inside the cells as a source of energy metabolism [57]. Glutaminolysis is also essential to providing high levels of energy required by HSCs to maintain the activated phenotype [59].…”

Section: Limitation Of Hsc Activationmentioning

confidence: 99%

Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression

Caligiuri

Gentilini

Pastore

et al. 2021

Cells

116

View full text Add to dashboard Cite

Chronic liver injury of different etiologies may result in hepatic fibrosis, a scar formation process consisting in altered deposition of extracellular matrix. Progression of fibrosis can lead to impaired liver architecture and function, resulting in cirrhosis and organ failure. Although fibrosis was previous thought to be an irreversible process, recent evidence convincingly demonstrated resolution of fibrosis in different organs when the cause of injury is removed. In the liver, due to its high regenerative ability, the extent of fibrosis regression and reversion to normal architecture is higher than in other tissues, even in advanced disease. The mechanisms of liver fibrosis resolution can be recapitulated in the following main points: removal of injurious factors causing chronic hepatic damage, elimination, or inactivation of myofibroblasts (through various cell fates, including apoptosis, senescence, and reprogramming), inactivation of inflammatory response and induction of anti-inflammatory/restorative pathways, and degradation of extracellular matrix. In this review, we will discuss the major cellular and molecular mechanisms underlying the regression of fibrosis/cirrhosis and the potential therapeutic approaches aimed at reversing the fibrogenic process.

show abstract

“…Focusing on HSCs, induction of apoptosis/senescence and reversion of activated HSCs are the main strategies [19]. Recent studies provide evidence that inhibition of aerobic glycolysis could attenuate the activation of HSCs [48,49]. Our findings suggest that the functional effects of STC1 in forming a feedforward loop to promote the fibrogenic process, partly via enhancing the glycolytic activity of HSCs.…”

Section: Discussionmentioning

confidence: 84%

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Chan

Hon

et al. 2022

The Journal of Pathology

View full text Add to dashboard Cite

Stanniocalcin 1 (STC1), a secreted protein, is upregulated in human cancers including hepatocellular carcinoma (HCC). While most HCCs develop from chronic liver disease, which involves progressive parenchymal injury and fibrosis, the role of STC1 in this preneoplastic stage remains poorly understood. In this study we investigated the clinical relevance and functional significance of secreted STC1 in liver fibrosis. To this end, the STC1 level was determined in the serum samples of chronic hepatitis B patients and correlated with the degree of liver fibrosis. Diagnostic performance of STC1 was analysed by area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. The results were compared with other well-characterised serum biomarkers for liver fibrosis: Aspartate transaminase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). The functional role of STC1 was interrogated by in vitro experiments using cell line models. Expression of fibrogenic markers was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results showed that the serum STC1 level in chronic hepatitis B patients was positively correlated with the degree of liver fibrosis and showed a stepwise increase in accordance with the severity of fibrosis. The AUROCs for detecting significant fibrosis (>9.0 kPa) and cirrhosis (>12.0 kPa) was 0.911 and 0.880, respectively. STC1 demonstrated a superior specificity and positive predictive value when compared to APRI and FIB-4. Consistent with this, STC1 was elevated in the liver tissues and sera of CCl 4 -treated mice showing marked liver fibrosis. In vitro, STC1 was secreted by the human hepatic stellate cell line LX2. Human recombinant STC1 (rhSTC1) induced expression of fibrogenic markers in LX2 cells. The profibrogenic phenotype conferred by rhSTC1 or TGF-β1 in LX2 cells could be attenuated using anti-STC1 antibody. Taken together, STC1 is a specific serum biomarker for HBV-associated liver fibrosis. STC1 functionally promotes liver fibrogenesis and is a potential actionable target.

show abstract

Costunolide reduces glycolysis-associated activation of hepatic stellate cells via inhibition of hexokinase-2

Cited by 23 publications

References 25 publications

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Contact Info

Product

Resources

About