RNA-seq data analysis of stimulated hepatocellular carcinoma cells treated with epigallocatechin gallate and fisetin reveals target genes and action mechanisms

Agioutantis, Panagiotis; Kotsikoris, Vasilios; Kolisis, Fragiskos N.; Loutrari, Heleni

doi:10.1016/j.csbj.2020.03.006

Cited by 9 publications

(8 citation statements)

References 55 publications

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“…Furthermore, the present results for IGF1R and MDM2 inhibitors corroborated those of a recent study on numerous cancer liver cell lines providing experimental evidence of an augmented efficacy of IGF1R inhibitor linsitinib as well as of MDM2 inhibitor nutlin-3 against liver cancer lines with prominent hepatoblast/hepatocyte-like characteristics [36], thus supporting the validity of our approach. Additionally, the natural compound epigallocatechin-3-monogallate was identified as being comparatively more effective against well-differentiated HCC lines, in full agreement with previous studies highlighting HEP3B and HEPG2 cell lines as particularly responsive against that nutraceutical [61,62].…”

Section: Discussionsupporting

confidence: 88%

Computational Analysis of Transcriptomic and Proteomic Data for Deciphering Molecular Heterogeneity and Drug Responsiveness in Model Human Hepatocellular Carcinoma Cell Lines

Agioutantis

Loutrari

Kolisis

2020

Genes

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Hepatocellular carcinoma (HCC) is associated with high mortality due to its inherent heterogeneity, aggressiveness, and limited therapeutic regimes. Herein, we analyzed 21 human HCC cell lines (HCC lines) to explore intertumor molecular diversity and pertinent drug sensitivity. We used an integrative computational approach based on exploratory and single-sample gene-set enrichment analysis of transcriptome and proteome data from the Cancer Cell Line Encyclopedia, followed by correlation analysis of drug-screening data from the Cancer Therapeutics Response Portal with curated gene-set enrichment scores. Acquired results classified HCC lines into two groups, a poorly and a well-differentiated group, displaying lower/higher enrichment scores in a “Specifically Upregulated in Liver” gene-set, respectively. Hierarchical clustering based on a published epithelial–mesenchymal transition gene expression signature further supported this stratification. Between-group comparisons of gene and protein expression unveiled distinctive patterns, whereas downstream functional analysis significantly associated differentially expressed genes with crucial cancer-related biological processes/pathways and revealed concrete driver-gene signatures. Finally, correlation analysis highlighted a diverse effectiveness of specific drugs against poorly compared to well-differentiated HCC lines, possibly applicable in clinical research with patients with analogous characteristics. Overall, this study expanded the knowledge on the molecular profiles, differentiation status, and drug responsiveness of HCC lines, and proposes a cost-effective computational approach to precision anti-HCC therapies.

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Section: Discussionsupporting

confidence: 88%

Computational Analysis of Transcriptomic and Proteomic Data for Deciphering Molecular Heterogeneity and Drug Responsiveness in Model Human Hepatocellular Carcinoma Cell Lines

Agioutantis

Loutrari

Kolisis

2020

Genes

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“…[31] CLIC3 was upregulated in HCC cells and was associated with a short OS and improved tumor cell migration and metastasis by regulating membrane ruffling, and may act as a novel target of epigallocatechin gallate and fisetin. [33,34] Flores-Tellez et al [35] showed that CLIC5 is upregulated in rat liver tumors, promoting tumor cell proliferation, migration potential, and invasion capacity, and was co-localized with podocalyxin, and CLIC5 in tumor regions. HCC develops owing to the abnormal regulation of multiple genetic, epigenetic, and signaling pathways that interact with the tumor microenvironment, promoting the occurrence, development, and metastasis of tumors.…”

Section: Discussionmentioning

confidence: 99%

Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis

et al. 2021

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“…Our results also indicted that fisetin could nullify the harmful effects of NDEA and thus tend to bring back the flies' behaviours to near normal. Fisetin, a bioactive flavonoid has been documented widely to inhibit the proliferation of various types of tumors in animals [53] and in various cancer cell lines [54]. The antitumor effects of fisetin could be mediated by modulating different signalling pathways in diverse frameworks [55].…”

Section: Discussionmentioning

confidence: 99%

Protective Influence of Fisetin on Cognitive and Biochemical Indices in N-Nitrosodietyhlamine Treated Drosophila Melanogaster

Sofia

Subramanian

2021

Int J Curr Pharm Sci

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Objective: The current investigation is intended to investigate the protecting influence of fisetin on cognitive, as well as biochemical indices in N-Nitrosodiethylamine (NDEA, a potent carcinogen), treated Drosophila melanogaster. Methods: D. melanogaster is used as a model organism for this investigation. Experimental flies are divided into four groups. Group 1–control, group 2-flies were treated with 0.01% NDEA in food medium, group 3–flies treated with 0.01% NDEA and 0.01% fisetin and group 4-flies were treated with 0.01% fisetin alone. Behavioural abnormalities (negative geotaxis, phototaxis, smell and taste chemotaxis, hygrotaxis and thermotaxis) were quantitatively observed to be deviated in NDEA treated flies compared to control but were tend to be normalized in fisetin treated flies. Results: The contents of protein carbonyl, thiobarbituric acid reactive substance (TBARS), protein thiol and lipid peroxides were noticeably augmented in NDEA treated flies than control flies and correspondingly tend to normalize in fisetin treated groups. Further, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidise (GPX) and reduced glutathione (GSH) were decreased in NDEA treated group and were significantly increased (p<0.05) in fisetin treated groups. Conclusion: Fisetin, a bioactive phytochemical could act as a potent antioxidant and as well exhibit antiproliferative characteristics. Our investigation indicates that this could prevent the abnormalities in behaviour and redox homeostasis during carcinogenesis in D. melanogaster.

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RNA-seq data analysis of stimulated hepatocellular carcinoma cells treated with epigallocatechin gallate and fisetin reveals target genes and action mechanisms

Cited by 9 publications

References 55 publications

Computational Analysis of Transcriptomic and Proteomic Data for Deciphering Molecular Heterogeneity and Drug Responsiveness in Model Human Hepatocellular Carcinoma Cell Lines

Computational Analysis of Transcriptomic and Proteomic Data for Deciphering Molecular Heterogeneity and Drug Responsiveness in Model Human Hepatocellular Carcinoma Cell Lines

Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis

Protective Influence of Fisetin on Cognitive and Biochemical Indices in N-Nitrosodietyhlamine Treated Drosophila Melanogaster

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