Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death

Li, Sainan; Li, Jingjing; Dai, Weiqi; Zhang, Qinghui; Jiao, Feng; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Chen, Kan; Xia, Yujing; Lü, Jie; Zhou, Yingqun; Fan, Xiaoming; Mo, Wenhui; Xu, Ling; Guo, Chuanyong

doi:10.1038/bjc.2017.323

Cited by 116 publications

(92 citation statements)

References 34 publications

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“…The protective effects of many Chinese herbal medicines, such as quercetin, [51][52][53] oleanolic acid, 54 proanthocyanidin B2, 55 epigallocatechin-3-gallate, 56 isorhamnetin 57 and genistein, 58 in liver diseases have been confirmed by our studies.…”

Section: Ppa Rγ Agonis Ts From Natur Al Produc Tssupporting

confidence: 79%

Therapeutic potential of PPARγ natural agonists in liver diseases

Guo

2020

J Cellular Molecular Medi

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Peroxisome proliferator‐activated receptor gamma (PPARγ) is a vital subtype of the PPAR family. The biological functions are complex and diverse. PPARγ plays a significant role in protecting the liver from inflammation, oxidation, fibrosis, fatty liver and tumours. Natural products are a promising pool for drug discovery, and enormous research effort has been invested in exploring the PPARγ‐activating potential of natural products. In this manuscript, we will review the research progress of PPARγ agonists from natural products in recent years and probe into the application potential and prospects of PPARγ natural agonists in the therapy of various liver diseases, including inflammation, hepatic fibrosis, non‐alcoholic fatty liver and liver cancer.

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Section: Ppa Rγ Agonis Ts From Natur Al Produc Tssupporting

confidence: 79%

Therapeutic potential of PPARγ natural agonists in liver diseases

Guo

2020

J Cellular Molecular Medi

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“…The results indicated that the first step rate limiting enzyme, glycolysis hexokinase (HK2), which is overexpressed in malignant cells, 34 had significantly decreased protein levels following co-treatment with PD and 2-DG ( Figure 5A,B). 35,36 In this study, we also found that a combination of PD and 2-DG inhibited the protein expression of HIFIα in 4T1 and MCF-7 cells (Figure 5A,B). In addition, we noticed an aberrant overexpression of hypoxia-inducible factor 1α (HIF1α) in many different cancers and HK-2 is one of its downstream transcriptional targets.…”

Section: The Synergistic Anti-cancer Effect Of Pd and 2-dg Is Throusupporting

confidence: 66%

“…In addition, we noticed an aberrant overexpression of hypoxia-inducible factor 1α (HIF1α) in many different cancers and HK-2 is one of its downstream transcriptional targets. 35,36 In this study, we also found that a combination of PD and 2-DG inhibited the protein expression of HIFIα in 4T1 and MCF-7 cells (Figure 5A,B). In addition, we also found that targeting HK2 with siRNA can block breast cancer cell survival and Figures 5C5-7).…”

Section: The Synergistic Anti-cancer Effect Of Pd and 2-dg Is Throusupporting

confidence: 66%

“…49 It is worth noting that the phosphorylation of AKT results in the upregulation of HIF1 in cancer cells. 52 In this study, this is evidenced by the silencing of HK2 by siRNA enhancing the inhibitory effect of combination treatment on glycolysis and growth ( Figure 5). The glycolysis rate strongly depends on the upregulated expression and activity of glucose transporters (Gluts), such as Glut1, which is regulated by HIF-1α and is considered the main overexpressed Glut, with a 10-12-fold higher expression in tumours than in normal cells.…”

Section: Discussionmentioning

confidence: 50%

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Targeting the ROS/PI3K/AKT/HIF‐1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2‐Deoxy‐d‐glucose

Zhang

Zhu

et al. 2019

J Cellular Molecular Medi

113

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It is well established that cancer cells depend upon aerobic glycolysis to provide the energy they need to survive and proliferate. However, anti‐glycolytic agents have yielded few positive results in human patients, in part due to dose‐limiting side effects. Here, we discovered the unexpected anti‐cancer efficacy of Polydatin (PD) combined with 2‐deoxy‐D‐glucose (2‐DG), which is a compound that inhibits glycolysis. We demonstrated in two breast cell lines (MCF‐7 and 4T1) that combination treatment with PD and 2‐DG induced cell apoptosis and inhibited cell proliferation, migration and invasion. Furthermore, we determined the mechanism of PD in synergy with 2‐DG, which decreased the intracellular reactive oxygen (ROS) levels and suppressed the PI3K/AKT pathway. In addition, the combined treatment inhibited the glycolytic phenotype through reducing the expression of HK2. HK2 deletion in breast cancer cells thus improved the anti‐cancer activity of 2‐DG. The combination treatment also resulted in significant tumour regression in the absence of significant morphologic changes in the heart, liver or kidney in vivo. In summary, our study demonstrates that PD synergised with 2‐DG to enhance its anti‐cancer efficacy by inhibiting the ROS/PI3K/AKT/HIF‐1α/HK2 signalling axis, providing a potential anti‐cancer strategy.

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“…Gen, as a soy-derived estrogenic compound, exhibits its beneficial effects: prevention of several types of cancers and cardiovascular diseases [26][27][28][29]. Gen exerts the therapeutic function in cardiovascular diseases through various mechanisms, including estrogenic activity [30], antioxidant [31], metabolism regulation [32], and so on.…”

Section: Discussionmentioning

confidence: 99%

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Shi¹,

Zhang²,

Hu³

et al. 2019

Pharmacology

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Background/Aims: Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury. Methods: Cobalt chloride (CoCl₂) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1α and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis. Results: In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1α was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl₂-induced cell death and suppressed HIF-1α expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl₂-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression. Conclusions: Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.

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Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death

Cited by 116 publications

References 34 publications

Therapeutic potential of PPARγ natural agonists in liver diseases

Therapeutic potential of PPARγ natural agonists in liver diseases

Targeting the ROS/PI3K/AKT/HIF‐1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2‐Deoxy‐d‐glucose

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

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