Ginsenoside compound K inhibits growth of lung cancer cells via HIF-1Î±-mediated glucose metabolism

Chen, Huafei; Wu, Lei; Li, Xiaofeng; Zhu, You‐cai; Wang, Wenxian; Xu, C.; Huang, Zhongyang; Du, Kun

doi:10.14715/cmb/2019.65.4.8

Cited by 23 publications

(19 citation statements)

References 25 publications

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“…Furthermore, the suppression of the growth of NSCLC cells was studied by targeting the metabolism of glucose. Compound K suppressed the levels of hypoxia-inducible factor 1-alpha and its downstream glucose transporter1 gene [ 83 ]. Another study showed the anti-cancer effect of CK against HepG2 cells and xenografted (HepG2) BALB/c nude mice.…”

Section: Health-promoting Activitiesmentioning

confidence: 99%

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Sharma

Lee

2020

Biomolecules

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Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.

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Section: Health-promoting Activitiesmentioning

confidence: 99%

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Sharma

Lee

2020

Biomolecules

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“…For example, Chen et al found that inhibiting the expression of HIF-1α decreased the GLUT1 expression level, and thus caused a reduction of the tumor volume and weight of LOVO cell line xenografts [42]. Some studies also have proposed that combined inhibition of HIF-1α and GLUT1 could be a promising cancer therapeutic strategy [43][44][45][46]. Our work demonstrated that PDQ is just one of the rst choice drugs that realize this antitumor effect.…”

Section: Discussionmentioning

confidence: 54%

“…which is associated with cancer cells proliferation and poor prognosis in tumors [9,10]. Studies have shown that ginsenoside can inhibit the growth of liver or lung cancers by inhibiting hypoxia-inducible factor-1α (HIF-1α) mediated glucose metabolism [11,12]. With the deepening of research, it is found that secondary ginsenosides and aglycones produced by degradation of ginsenosides have stronger pharmacological effects [13].…”

Section: Introductionmentioning

confidence: 99%

The Antitumor Activity of Pseudoginsengenin DQ Against Hypopharyngeal Cancer Cells via Targeting HIF-1α-GLUT1 Pathway

Wang¹,

Cai²,

Feng³

et al. 2021

Preprint

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Background The ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside Protopanaxadiol (PPD), the octanone Pseudoginsengenin DQ (PDQ) may have stronger pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumor activity and molecular mechanism against hypopharyngeal cancer cells remains unclear. Methods Cell Counting Kit-8, cell cycle assay and cell apoptosis assay were conducted to detect FADU cells proliferation, cell phase and apoptosis. The interactions between PDQ and HIF-1α were investigated by a molecular docking study. The expression of HIF-1α, GLUT1, apoptosis related proteins was tested by western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. Glucose uptake assay was used to assess the glucose uptake capacity of FADU cells. Results PDQ was found to suppress the proliferation, reduce glucose uptake, induce the cell cycle arrest and apoptosis of FaDu cells. Molecular docking study demonstrated that PDQ could interact with the active site of HIF-1α. PDQ decreased the expression and mRNA levels of HIF-1α and its downstream factor GLUT1. Moreover, dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane but also inhibited its clustering. Conclusion Our work elucidated that the antitumor effect of PDQ is related to its downregulation of HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.

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“…In addition to the high energy requirements of enhanced proliferation, cell division also requires large amounts of biomolecules, including nucleic acids and lipids, for which glucose is an important biosynthetic precursor. Enhanced levels of glucose transporters and enzymes in the glycolytic pathway and upregulated lactate level are often found in NSCLC cells, and inhibition of aerobic glycolysis arrests cancer cell proliferation ( 11 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

Deoxypodophyllotoxin Inhibits Non-Small Cell Lung Cancer Cell Growth by Reducing HIF-1α-Mediated Glycolysis

et al. 2021

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Cancer cell proliferation is a metabolically demanding process that requires high rate of glycolysis to support anabolic growth. Deoxypodophyllotoxin (DPT) is a natural flavonolignan with various pharmacological activities, including antitumor effect. However, whether DPT affects the metabolic reprogramming of cancer cells is unknown. The purpose of this study is to investigate the role of DPT on non-small cell lung cancer (NSCLC) and to explore whether HIF-1α-mediated glycolysis is involved in its mechanism of action.The level of HIF-1α mRNA and protein in NSCLC cells following DPT treatment was detected using qRT-PCR and western blotting, respectively. Cell Counting Kit-8 (CCK-8) and caspase-3 activity assays were performed to analyze cell proliferation and apoptosis. The underlying molecular mechanism was identified by dual luciferase assay, Western blotting, qRT-PCR, glucose consumption, lactate production, and immunoprecipitation. A murine NSCLC model was used to clarify the effect of DPT treatment on tumor cell proliferation. Our findings showed that DPT treatment inhibited NSCLC cell growth in a dose- and time-dependent manner. Further analysis suggested that DPT treatment inhibited HIF-1α signaling pathway by Parkin-mediated protein degradation in NSCLC cells. DPT treatment significantly decreased glucose consumption and lactate production. In addition, DPT treatment reduced the expression of HIF-1α target genes, including GLUT1, HK2 and LDHA, resulting in reduction in glycolysis. We further revealed that DPT-induced cell growth inhibition and increased glucose and lactate levels could be reversed by overexpressing HIF-1α. Additionally, we found that DPT repressed NSCLC growth and GLUT1, HK2 and LDHA expression in vivo. Overall, this study suggested that DPT inhibited NSCLC growth by preventing HIF-1α-mediated glycolysis.

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Ginsenoside compound K inhibits growth of lung cancer cells via HIF-1Î±-mediated glucose metabolism

Cited by 23 publications

References 25 publications

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

The Antitumor Activity of Pseudoginsengenin DQ Against Hypopharyngeal Cancer Cells via Targeting HIF-1α-GLUT1 Pathway

Deoxypodophyllotoxin Inhibits Non-Small Cell Lung Cancer Cell Growth by Reducing HIF-1α-Mediated Glycolysis

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