By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice

Dai, Weiqi; Wang, Fan; Lü, Jie; Xia, Yujing; He, Lei; Chen, Kan; Li, Jingjing; Li, Sainan; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Abudumijiti, Huerxidan; Chen, Rongxia; Zhang, Rong; Zhou, Li; Zhou, Zheng; Zhu, Rong; Yang, Jing; Wang, Chengfen; Zhang, Huawei; Zhou, Yingqun; Xu, Ling; Guo, Chuanyong

doi:10.18632/oncotarget.3800

Cited by 99 publications

(105 citation statements)

References 45 publications

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“…Saline, sorafenib (10 mg/kg)5152, EGCG (10 mg/kg)53, and sorafenib (10 mg/kg) + EGCG (10 mg/kg) were used for the in vivo experiments.…”

Section: Resultsmentioning

confidence: 99%

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In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

Jiao

et al. 2016

Sci Rep

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Glycolysis, as an altered cancer cell-intrinsic metabolism, is an essential hallmark of cancer. Phosphofructokinase (PFK) is a metabolic sensor in the glycolytic pathway, and restricting the substrate availability for this enzyme has been researched extensively as a target for chemotherapy. In the present study, we investigated that the effects of epigallocatechin-3-gallate (EGCG), an active component of green tea, on inhibiting cell growth and inducing apoptosis by promoting a metabolic shift away from glycolysis in aerobic glycolytic hepatocellular carcinoma (HCC) cells. EGCG modulated the oligomeric structure of PFK, potentially leading to metabolic stress associated apoptosis and suggesting that EGCG acts by directly suppressing PFK activity. A PFK activity inhibitor enhanced the effect, while the allosteric activator reversed EGCG-induced HCC cell death. PFK siRNA knockdown-induced apoptosis was not reversed by the activator. EGCG enhanced the effect of sorafenib on cell growth inhibition in both aerobic glycolytic HCC cells and in a xenograft mouse model. The present study suggests a potential role for EGCG as an adjuvant in cancer therapy, which merits further investigation at the clinical level.

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“…Saline, sorafenib (10 mg/kg)5152, EGCG (10 mg/kg)53, and sorafenib (10 mg/kg) + EGCG (10 mg/kg) were used for the in vivo experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Sorafenib is the only drug approved for the treatment of HCC505152. However, the low rate of tolerance to sorafenib among HCC patients limits its benefits75.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

Jiao

et al. 2016

Sci Rep

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“…and transfected as described elsewhere [23, 24]. The target sequences of the shRNAs were listed in Supplementary Table 5.…”

Section: Methodsmentioning

confidence: 99%

UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2

Bai

Long

et al. 2016

Oncotarget

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The ubiquitin-dependent proteasomal degradation of proteins controls signaling and cellular survival. In this study, we found that ubiquitin associated protein 2 (UBAP2) was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, higher expression of UBAP2 in cancer tissues was correlated with good prognosis in HCC patients. Knockdown of UBAP2 significantly enhanced the invasion and proliferation of HCC cells in vitro and promoted tumor growth in vivo, while enforced expression of UBAP2 impaired the aggressive ability and tumor growth of HCC cells. Mechanistically, UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination, and then inhibited HCC progression. Collectively, UBAP2 appears as a novel marker for predicting prognosis and a therapeutic target for HCC.

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“…RSV was proved to protect hepatic antioxidant systems against ischemia reperfusioninduced oxidative stress, protect from peroxynitrite and oxidative DNA damage caused by hydrogen peroxide [107]. Malondialdehyde (MDA), that is a lipid peroxidation end-product, connect to the cross and Generate to modification in ion permeability and enzyme activity [108][109][110]. The oxidative stress and lipid peroxidation are evaluated by MDA level.…”

Section: Resveratrolmentioning

confidence: 99%

Reduction of Hepatotoxicity Induced by Doxorubicin

Bengaied¹,

Ribeiro²,

Amri³

et al. 2017

J Integr Oncol

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Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance.Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DO x .

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By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice

Cited by 99 publications

References 45 publications

In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2

Reduction of Hepatotoxicity Induced by Doxorubicin

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