Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats

Huang, Hongwu; Liu, Zhenzhen; Qi, Xiaoru; Gao, Nailong; Chang, Junbiao; Yang, Miaomiao; Sha, Na; Liu, Yanyan; Song, Rui; Li, Lü; Chen, Guangliang; Zhou, Hui

doi:10.1016/j.jep.2021.114479

Cited by 3 publications

(3 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nearly all types of cancer cells appear to overexpress PKM2 to promote aerobic glycolysis and give tumor cells a proliferative advantage over healthy tissue [38][39][40][41]. We found that the AFC downregulated the kinase in HCT116 and LoVo colon cancer cell lines in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 83%

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

Liu,

Xing,

Guo

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Aerobic glycolysis contributes to the high rate of metabolism in tumour cells and colorectal cancer is one of the highly metabolic malignancies. Highly expressed M2-type pyruvate kinase (PKM2) promotes tumour cell proliferation and migration as the rate-limiting enzyme of aerobic glycolysis. Previously we have shown that the active fraction from clove (AFC) can inhibit the growth of colon cancer cells in vitro. However, the mechanism of action regarding the anti-colon cancer activity of AFC, especially in aerobic glycolysis, has not been adequately investigated. Methods In vitro anti-colon cancer activity was assessed by CCK8 assay and colony formation assay, and changes in aerobic glycolytic capacity were assessed by evaluating changes in glucose consumption, lactate production, pyruvate kinase activity and pyruvate production. HCT116 cells xenograft model in nude mice was established to measure the anti-colon cancer activity of AFC in vivo. Mechanism of action studies involved western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown transfection, and immunohistochemistry. Results The present study confirmed those findings by showing that the active fraction significantly inhibited the growth of five lines of colon cancer cells (HT29, SW620, Caco-2, HCT116 and LoVo). And we found that the active fraction reduced pyruvate kinase activity, glucose uptake, and production of pyruvate and lactate. It also downregulated M2-type pyruvate kinase (PKM2), c-myc and cyclin D1. Knockdown of PKM2 on its own mimicked the effects of active fraction, which could result in the ability to inhibit cell proliferation and aerobic glycolysis. Consistent with these results in cell culture, the active fraction significantly inhibited tumor growth and downregulated PKM2, c-myc and cyclin D1 in HCT116 xenografts in mice, while causing milder liver damage and weight loss than the conventional chemotherapeutic 5-fluorouracil (5-FU). Conclusion Our fndings indicate that AFC inhibits colon cancer growth by downregulating PKM2 to inhibit aerobic glycolysis and reduces tumour-specific high expression of c-myc and cyclin D1. Future work should explore how it downregulates pyruvate kinase in the first place, and the intrinsic mechanism between the down-regulation of PKM2 and the down-regulation of c-myc and cyclin D1.

show abstract

Section: Resultsmentioning

confidence: 83%

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

Liu,

Xing,

Guo

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“… 2020 ; Huang H et al. 2021 ; Gao and Nan 2022 ). Rhubarb possesses a number of active ingredients, such as anthraquinone, anthrone, organic acid, tannin and polysaccharides.…”

Section: Introductionmentioning

confidence: 99%

Physcion inhibition of CYP2C9, 2D6 and 3A4 in human liver microsomes

Liu,

Sun,

2024

Pharmaceutical Biology

View full text Add to dashboard Cite

Context The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities. Objectives The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use. Materials and methods The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed. Results Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC 50 values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the K i values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a K i value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the K I and K inact parameters of 3.10 μM −1 and 0.049 min −1 , respectively. Conclusions The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.

show abstract

“…Rhei Radix et Rhizoma (Rhubarb) is the dried root and rhizome of genus Rheum (Polygonaceae), which has been widely used as a traditional medicine for two thousand years in China and Asian countries [6]. Current studies have shown that rhubarb has many pharmacological activities, such as fecal softening, lipid regulating and anti-inflammatory effect so on [7,8]. The extract of rhubarb has been made into different supplementary food in the prevention of obesity, and rhubarb-free anthraquinones (RhA) consisted of aloeemodin, rhein, emodin, chrysophanol and physion are the major components of rhubarb extract [9], which may be responsible for its anti-obesity effect [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Rhubarb Free Anthraquinones on Obesity in Rats and Its Potential Mechanism

ZHANG,

WANG,

KHATTAK

et al. 2023

Int J App Pharm

View full text Add to dashboard Cite

Objective: The study was to confirm the effect of rhubarb-free anthraquinones (RhA) on anti-obesity and preliminarily explore the possible mechanism of action of RhA. Methods: The obesity model of rats was induced by a high-fat diet to evaluate the effect of RhA on weight reduction and their potential mechanism based on network pharmacology and molecular docking as well as Western blotting analysis. Results: RhA significantly reduced body weight, lipid-body ratio and Lee's index of the obese model rats. The level of low-density lipoprotein cholesterol significantly was decreased, and the number of fat droplets and fat cells in the liver tissue of the obese model rats was significantly reduced after treatment. The anti-obesity-related core proteins mainly targeted by RhA were predicted as MAPK8, MAPK14 and CASP3. Aloe-emodin, rhein, emodin, chrysophanol, and physcion had high affinity with these proteins. The relative expression of CASP3 and MAPK8 in the obese model rats was increased at gene and proteins levels after treatment. Conclusion: RhA had significant weight-reducing and blood lipid-lowering effect of obese rats, and they may mainly intervene in obesity by up-regulating the expression levels of MAPK8 and CASP3 protein involved in fat metabolism.

show abstract

Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats

Cited by 3 publications

References 54 publications

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

Physcion inhibition of CYP2C9, 2D6 and 3A4 in human liver microsomes

Effect of Rhubarb Free Anthraquinones on Obesity in Rats and Its Potential Mechanism

Contact Info

Product

Resources

About