Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study

Sabry, Dina; Abdelaleem, Omayma O; Ali, Amani; Mohammed, Rehab Ahmed; Abdel-Hameed, Nehal D; Hassouna, Amira; Khalifa, Warda A

doi:10.1007/s11033-019-04653-6

Cited by 30 publications

(20 citation statements)

References 49 publications

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“…EGCG also downregulated lncRNA-AF085935 in HCC cells. It was suggested that lncRNA-AF085935 promoted proliferation of HCC cells [69]. However, the study did not clearly provide a link between lncRNA-AF085935 and its targets and how lncRNA-AF085935 regulated apoptosis and proliferation in HCC cells.…”

Section: Targeting Of Oncogenic Lncrnasmentioning

confidence: 88%

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Farooqi

Pinheiro

Granja

et al. 2020

Cancers

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Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.

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Section: Targeting Of Oncogenic Lncrnasmentioning

confidence: 88%

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Farooqi

Pinheiro

Granja

et al. 2020

Cancers

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“…Moreover, it was found that GPC3, SULF2, and lncRNA-A F085935 were implicated in the proliferation of HCC with bad prognosis when overexpressed [ 25 , 33 ]. Therefore, our results provide a novel insight to clarify the anticancer capability of chrysin against HCC via GPC3/SULF2 axis and lncRNA-A F085935 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, many researchers proposed GPC3 as the target of effective cytotoxic agents against HCC [ 25 , 26 , 43 ]. Epigallocatechin-3-gallate, a polyphenol of the natural product green tea, in addition to sodium ascorbate, a form of vitamin C, was recently reported to exert their antiproliferative action against HCC through a marked reduction in GPC3 protein expression [ 25 , 33 ]. Similarly, the results of this study revealed that chrysin alone and its combination with cisplatin markedly reduced cellular GPC3 protein, immunostaining, as well as mRNA expressions in HepG2 cells, compared to untreated HepG2 cells in a dose- and time-dependent manner, confirming the involvement of GPC3 suppression as a novel antiproliferative mechanism for chrysin against HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, lncRNA–AF085935 is transcribed in antisense orientation with respect to GPC3. Moreover, lncRNA–AF085935 was upregulated and coexpressed with GPC3 in HCC cells and tissues [ 33 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…These dysregulated lncRNAs are strongly suggested as novel diagnostic biomarkers and/or therapeutic targets for HCC [ 32 ]. Specifically, the lncRNA-AF085935 was highly expressed in HCC and could be used as a vital biomarker for HCC [ 33 ]. This study was carried out to discover a new insight of the antiproliferative action of chrysin alone or with its concurrent treatment with cisplatin against HCC through the impact on the GPC3/SULF2 axis in addition to lncRNA-AF085935 expression.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression

Sherif

Al-Mutabagani

Sabry

et al. 2020

IJMS

Self Cite

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The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner.

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A novel strategy for the diagnosis, prognosis, treatment, and chemoresistance of hepatocellular carcinoma: DNA methylation

Liu

Peng

et al. 2020

Medicinal Research Reviews

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The cancer mortality rate of hepatocellular carcinoma (HCC) is the second highest in the world and the therapeutic options are limited. The incidence of this deadly cancer is rising at an alarming rate because of the high degree of resistance to chemo‐ and radiotherapy, lack of proper, and adequate vaccination to hepatitis B, and lack of consciousness and knowledge about the disease itself and the lifestyle of the people. DNA methylation and DNA methylation‐induced epigenetic alterations, due to their potential reversibility, open the access to develop novel biomarkers and therapeutics for HCC. The contribution to these epigenetic changes in HCC development still has not been thoroughly summarized. Thus, it is necessary to better understand the new molecular targets of HCC epigenetics in HCC diagnosis, prevention, and treatment. This review elaborates on recent key findings regarding molecular biomarkers for HCC early diagnosis, prognosis, and treatment. Currently emerging epigenetic drugs for the treatment of HCC are summarized. In addition, combining epigenetic drugs with nonepigenetic drugs for HCC treatment is also mentioned. The molecular mechanisms of DNA methylation‐mediated HCC resistance are reviewed, providing some insights into the difficulty of treating liver cancer and anticancer drug development.

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Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study

Cited by 30 publications

References 49 publications

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression

A novel strategy for the diagnosis, prognosis, treatment, and chemoresistance of hepatocellular carcinoma: DNA methylation

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