The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress
Background There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor...
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| Veröffentlicht in: | Molecular biology reports 2023, Vol.50 (1), p.77-84 |
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| creator | Moghadam, Delaram Zarei, Reza Vakili, Sina Ghojoghi, Rozita Zarezade, Vahid Veisi, Ali Sabaghan, Mohamad Azadbakht, Omid Behrouj, Hamid |
| description | Background
There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma.
Methods
The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers.
Results
The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it.
Conclusions
This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced. |
| doi_str_mv | 10.1007/s11033-022-08031-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2849888511</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2770372109</sourcerecordid><originalsourceid>FETCH-LOGICAL-c408t-524829ca46503215016a8c856cf92a787bc48b030f0d93cc5e9494e2917be9043</originalsourceid><addsrcrecordid>eNqFks1u1DAUhSMEokPhBVggS2yK1FD_ZeywQ1WZVlQgDWEdeZybiSuPHWyndN6Zh8DpFJBYwMrS9XfOvdc-RfGS4LcEY3EWCcGMlZjSEkvMSCkeFQtSCVbyWsjHxQIzTEouK3JUPIvxBmPMiaieFkdsybBYUrYofjQDIOh70An5HjmVpqAsGr3djwM4byNaQ7yFoFLw9hStlLVGI6VNd4qU69DHKfidcsYhPVgfTAfIOzRMuYYSWL_L0ggoQPbIZwrKRR3MmObqydBcrJs3CO7GADGarMxGlzCuKBpgVMlrsHayKiCtgjYut3qH8iAwD_vlat2Qs0-hpyiarVPWuC3KouG72t_P5u9Mp5K5BRTT7P-8eNIrG-HFw3lcfP1w0ZxfltefV1fn769LzbFMZUW5pLVWfFlhRkmFyVJJLaul7muqhBQbzeUmP26Pu5ppXUHNaw60JmIDNebsuDg5-I7Bf5sgpnZn4ryJcuCn2FLJaynzv5D_o4LlGbCULKOv_0Jv_BTy2jMlMBOU4DpT9EDp4GMM0LdjMDsV9i3B7Ryb9hCbNsemvY9NK7Lo1YP1tNlB91vyKycZYAcg5iu3hfCn9z9sfwJ5jc_u</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2770372109</pqid></control><display><type>article</type><title>The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Moghadam, Delaram ; Zarei, Reza ; Vakili, Sina ; Ghojoghi, Rozita ; Zarezade, Vahid ; Veisi, Ali ; Sabaghan, Mohamad ; Azadbakht, Omid ; Behrouj, Hamid</creator><creatorcontrib>Moghadam, Delaram ; Zarei, Reza ; Vakili, Sina ; Ghojoghi, Rozita ; Zarezade, Vahid ; Veisi, Ali ; Sabaghan, Mohamad ; Azadbakht, Omid ; Behrouj, Hamid</creatorcontrib><description>Background
There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma.
Methods
The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers.
Results
The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it.
Conclusions
This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-022-08031-7</identifier><identifier>PMID: 36307623</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Acids ; Animal Anatomy ; Animal Biochemistry ; antineoplastic activity ; Biomedical and Life Sciences ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; cell lines ; Cell viability ; Chloride ; Chlorides ; dose response ; dyes ; Gallic acid ; Gallic Acid - pharmacology ; genes ; Hepatocellular carcinoma ; hepatoma ; Histology ; Humans ; Life Sciences ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Morphology ; neoplasm cells ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; NRF2 protein ; Original Article ; Oxidative Stress ; Polyphenols ; Polyphenols - pharmacology ; quantitative polymerase chain reaction ; Resveratrol ; Resveratrol - pharmacology ; RNA-directed DNA polymerase ; Signal Transduction ; SIRT1 protein ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; spectral analysis ; Spectrophotometry ; Telomerase ; Telomerase - genetics ; Telomerase - metabolism ; Telomerase reverse transcriptase</subject><ispartof>Molecular biology reports, 2023, Vol.50 (1), p.77-84</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-524829ca46503215016a8c856cf92a787bc48b030f0d93cc5e9494e2917be9043</citedby><cites>FETCH-LOGICAL-c408t-524829ca46503215016a8c856cf92a787bc48b030f0d93cc5e9494e2917be9043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-022-08031-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-022-08031-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36307623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moghadam, Delaram</creatorcontrib><creatorcontrib>Zarei, Reza</creatorcontrib><creatorcontrib>Vakili, Sina</creatorcontrib><creatorcontrib>Ghojoghi, Rozita</creatorcontrib><creatorcontrib>Zarezade, Vahid</creatorcontrib><creatorcontrib>Veisi, Ali</creatorcontrib><creatorcontrib>Sabaghan, Mohamad</creatorcontrib><creatorcontrib>Azadbakht, Omid</creatorcontrib><creatorcontrib>Behrouj, Hamid</creatorcontrib><title>The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>Background
There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma.
Methods
The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers.
Results
The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it.
Conclusions
This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.</description><subject>Acids</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>antineoplastic activity</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>cell lines</subject><subject>Cell viability</subject><subject>Chloride</subject><subject>Chlorides</subject><subject>dose response</subject><subject>dyes</subject><subject>Gallic acid</subject><subject>Gallic Acid - pharmacology</subject><subject>genes</subject><subject>Hepatocellular carcinoma</subject><subject>hepatoma</subject><subject>Histology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Morphology</subject><subject>neoplasm cells</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NRF2 protein</subject><subject>Original Article</subject><subject>Oxidative Stress</subject><subject>Polyphenols</subject><subject>Polyphenols - pharmacology</subject><subject>quantitative polymerase chain reaction</subject><subject>Resveratrol</subject><subject>Resveratrol - pharmacology</subject><subject>RNA-directed DNA polymerase</subject><subject>Signal Transduction</subject><subject>SIRT1 protein</subject><subject>Sirtuin 1 - genetics</subject><subject>Sirtuin 1 - metabolism</subject><subject>spectral analysis</subject><subject>Spectrophotometry</subject><subject>Telomerase</subject><subject>Telomerase - genetics</subject><subject>Telomerase - metabolism</subject><subject>Telomerase reverse transcriptase</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFks1u1DAUhSMEokPhBVggS2yK1FD_ZeywQ1WZVlQgDWEdeZybiSuPHWyndN6Zh8DpFJBYwMrS9XfOvdc-RfGS4LcEY3EWCcGMlZjSEkvMSCkeFQtSCVbyWsjHxQIzTEouK3JUPIvxBmPMiaieFkdsybBYUrYofjQDIOh70An5HjmVpqAsGr3djwM4byNaQ7yFoFLw9hStlLVGI6VNd4qU69DHKfidcsYhPVgfTAfIOzRMuYYSWL_L0ggoQPbIZwrKRR3MmObqydBcrJs3CO7GADGarMxGlzCuKBpgVMlrsHayKiCtgjYut3qH8iAwD_vlat2Qs0-hpyiarVPWuC3KouG72t_P5u9Mp5K5BRTT7P-8eNIrG-HFw3lcfP1w0ZxfltefV1fn769LzbFMZUW5pLVWfFlhRkmFyVJJLaul7muqhBQbzeUmP26Pu5ppXUHNaw60JmIDNebsuDg5-I7Bf5sgpnZn4ryJcuCn2FLJaynzv5D_o4LlGbCULKOv_0Jv_BTy2jMlMBOU4DpT9EDp4GMM0LdjMDsV9i3B7Ryb9hCbNsemvY9NK7Lo1YP1tNlB91vyKycZYAcg5iu3hfCn9z9sfwJ5jc_u</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Moghadam, Delaram</creator><creator>Zarei, Reza</creator><creator>Vakili, Sina</creator><creator>Ghojoghi, Rozita</creator><creator>Zarezade, Vahid</creator><creator>Veisi, Ali</creator><creator>Sabaghan, Mohamad</creator><creator>Azadbakht, Omid</creator><creator>Behrouj, Hamid</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>2023</creationdate><title>The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress</title><author>Moghadam, Delaram ; Zarei, Reza ; Vakili, Sina ; Ghojoghi, Rozita ; Zarezade, Vahid ; Veisi, Ali ; Sabaghan, Mohamad ; Azadbakht, Omid ; Behrouj, Hamid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-524829ca46503215016a8c856cf92a787bc48b030f0d93cc5e9494e2917be9043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acids</topic><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>antineoplastic activity</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>cell lines</topic><topic>Cell viability</topic><topic>Chloride</topic><topic>Chlorides</topic><topic>dose response</topic><topic>dyes</topic><topic>Gallic acid</topic><topic>Gallic Acid - pharmacology</topic><topic>genes</topic><topic>Hepatocellular carcinoma</topic><topic>hepatoma</topic><topic>Histology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Morphology</topic><topic>neoplasm cells</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NRF2 protein</topic><topic>Original Article</topic><topic>Oxidative Stress</topic><topic>Polyphenols</topic><topic>Polyphenols - pharmacology</topic><topic>quantitative polymerase chain reaction</topic><topic>Resveratrol</topic><topic>Resveratrol - pharmacology</topic><topic>RNA-directed DNA polymerase</topic><topic>Signal Transduction</topic><topic>SIRT1 protein</topic><topic>Sirtuin 1 - genetics</topic><topic>Sirtuin 1 - metabolism</topic><topic>spectral analysis</topic><topic>Spectrophotometry</topic><topic>Telomerase</topic><topic>Telomerase - genetics</topic><topic>Telomerase - metabolism</topic><topic>Telomerase reverse transcriptase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moghadam, Delaram</creatorcontrib><creatorcontrib>Zarei, Reza</creatorcontrib><creatorcontrib>Vakili, Sina</creatorcontrib><creatorcontrib>Ghojoghi, Rozita</creatorcontrib><creatorcontrib>Zarezade, Vahid</creatorcontrib><creatorcontrib>Veisi, Ali</creatorcontrib><creatorcontrib>Sabaghan, Mohamad</creatorcontrib><creatorcontrib>Azadbakht, Omid</creatorcontrib><creatorcontrib>Behrouj, Hamid</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Molecular biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moghadam, Delaram</au><au>Zarei, Reza</au><au>Vakili, Sina</au><au>Ghojoghi, Rozita</au><au>Zarezade, Vahid</au><au>Veisi, Ali</au><au>Sabaghan, Mohamad</au><au>Azadbakht, Omid</au><au>Behrouj, Hamid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2023</date><risdate>2023</risdate><volume>50</volume><issue>1</issue><spage>77</spage><epage>84</epage><pages>77-84</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>Background
There is evidence that low doses or physiological concentrations of certain natural polyphenols enhance the activity of telomerase. However, the precise mechanism by which natural polyphenols regulate telomerase activity remains unclear. Recent research indicates that NF-E2 related factor 2 (Nrf2) and silent information regulator 1 (SIRT1) are involved in human telomerase reverse transcriptase (hTERT) regulation. Thus, in order to better comprehend the mechanism by which polyphenols regulate hTERT, the present study investigated the effects of the natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on hTERT, Nrf2, and SIRT1 expression as well as oxidative stress in HepG2 hepatocellular carcinoma.
Methods
The trypan blue dye exclusion assay was used to assess cell viability. The level of mRNA for hTERT, Nrf2, and SIRT1 was then determined using real-time PCR. A spectrophotometric analysis was conducted to quantify oxidative stress markers.
Results
The results demonstrated that Resveratrol induces the expression of hTERT and the SIRT1/Nrf2 pathway in a dose-dependent manner. Gallic acid at concentrations of 10 and 20 μM also increased the expression of the hTERT and SIRT1/Nrf2 pathway. Furthermore, dose-dependent overexpression of hTERT and Nrf2 was induced by Kuromanin chloride at 10 and 20 µM. Moreover, we found that Resveratrol and Kuromanin chloride ameliorated oxidative stress, whereas Gallic acid exacerbated it.
Conclusions
This study demonstrates that low doses of polyphenols (Resveratrol, Gallic acid, and Kuromanin chloride) upregulate the expression of the hTERT gene in the HepG2 hepatocellular carcinoma cell line, possibly via induction of the SIRT1/Nrf2 signaling pathway. Therefore, by targeting this pathway or hTERT, the anti-cancer effect of polyphenols can be enhanced.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>36307623</pmid><doi>10.1007/s11033-022-08031-7</doi><tpages>8</tpages></addata></record> |
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| ispartof | Molecular biology reports, 2023, Vol.50 (1), p.77-84 |
| issn | 0301-4851 1573-4978 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2849888511 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Acids Animal Anatomy Animal Biochemistry antineoplastic activity Biomedical and Life Sciences Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology cell lines Cell viability Chloride Chlorides dose response dyes Gallic acid Gallic Acid - pharmacology genes Hepatocellular carcinoma hepatoma Histology Humans Life Sciences Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - genetics Liver Neoplasms - pathology Morphology neoplasm cells NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism NRF2 protein Original Article Oxidative Stress Polyphenols Polyphenols - pharmacology quantitative polymerase chain reaction Resveratrol Resveratrol - pharmacology RNA-directed DNA polymerase Signal Transduction SIRT1 protein Sirtuin 1 - genetics Sirtuin 1 - metabolism spectral analysis Spectrophotometry Telomerase Telomerase - genetics Telomerase - metabolism Telomerase reverse transcriptase |
| title | The effect of natural polyphenols Resveratrol, Gallic acid, and Kuromanin chloride on human telomerase reverse transcriptase (hTERT) expression in HepG2 hepatocellular carcinoma: role of SIRT1/Nrf2 signaling pathway and oxidative stress |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T16%3A17%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effect%20of%20natural%20polyphenols%20Resveratrol,%20Gallic%20acid,%20and%20Kuromanin%20chloride%20on%20human%20telomerase%20reverse%20transcriptase%20(hTERT)%20expression%20in%20HepG2%20hepatocellular%20carcinoma:%20role%20of%20SIRT1/Nrf2%20signaling%20pathway%20and%20oxidative%20stress&rft.jtitle=Molecular%20biology%20reports&rft.au=Moghadam,%20Delaram&rft.date=2023&rft.volume=50&rft.issue=1&rft.spage=77&rft.epage=84&rft.pages=77-84&rft.issn=0301-4851&rft.eissn=1573-4978&rft_id=info:doi/10.1007/s11033-022-08031-7&rft_dat=%3Cproquest_cross%3E2770372109%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2770372109&rft_id=info:pmid/36307623&rfr_iscdi=true |