Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR)

BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glyc...

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Published in:Medical science monitor 2018-05, Vol.24, p.3283-3292
Main Authors: Liao, Weirong, Liu, Jingtian, Zhang, Dawei, Huang, Wenhai, Chen, Runhao
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Chalcones - pharmacology
Glycolysis - drug effects
Hexokinase - metabolism
Humans
Lab/In Vitro Research
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Receptor, Epidermal Growth Factor - metabolism
Signal Transduction - drug effects
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container_title Medical science monitor
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creator Liao, Weirong
Liu, Jingtian
Zhang, Dawei
Huang, Wenhai
Chen, Runhao
description BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro. The effect of butein on tumor glycolysis was determined by examining the changes in glucose uptake and lactate production. Hexokinase-2 (HK-2) expression in HCC cells upon butein treatment was analyzed by Western blotting. The activity of butein on EGFR signaling pathway was studied and its potency in EGFR exogenous overexpression cells was investigated. RESULTS After butein treatment, HCC cell proliferation was significantly inhibited (91.4% in Hep3B and 88.2% in Huh-7 at 80 μM, p
doi_str_mv 10.12659/MSM.906528
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Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro. The effect of butein on tumor glycolysis was determined by examining the changes in glucose uptake and lactate production. Hexokinase-2 (HK-2) expression in HCC cells upon butein treatment was analyzed by Western blotting. The activity of butein on EGFR signaling pathway was studied and its potency in EGFR exogenous overexpression cells was investigated. RESULTS After butein treatment, HCC cell proliferation was significantly inhibited (91.4% in Hep3B and 88.2% in Huh-7 at 80 μM, p&lt;0.001). Moreover, the number of colonies formed in the agar was substantially decreased (93.8% in Hep3B and 72.3% in Huh-7 at 80 μM, p&lt;0.001). With the suppression of HK-2 expression, glucose consumption in Hep3B and Huh-7 cells decreased by 48.4% and 56.3%, respectively (p&lt;0.01), and the lactate production also was reduced accordingly (39.5% in Hep3B and 48.6% in Huh-7, p&lt;0.01). Mechanism investigations demonstrated that butein dose-dependently blocked the activation of the EGFR signaling pathway in HCC cells. In EGFR exogenous overexpression cells, the glycolysis suppression exerted by butein was substantially attenuated. CONCLUSIONS Butein has a substantial inhibitory effect on tumor glycolysis in HCC cells, and the glycolysis suppression exerted by butein is closely related to its effect on the EGFR signaling pathway.</description><identifier>ISSN: 1643-3750</identifier><identifier>ISSN: 1234-1010</identifier><identifier>EISSN: 1643-3750</identifier><identifier>DOI: 10.12659/MSM.906528</identifier><identifier>PMID: 29777095</identifier><language>eng</language><publisher>United States: International Scientific Literature, Inc</publisher><subject>Apoptosis - drug effects ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chalcones - pharmacology ; Glycolysis - drug effects ; Hexokinase - metabolism ; Humans ; Lab/In Vitro Research ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Receptor, Epidermal Growth Factor - metabolism ; Signal Transduction - drug effects</subject><ispartof>Medical science monitor, 2018-05, Vol.24, p.3283-3292</ispartof><rights>Med Sci Monit, 2018 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-1ecf3c61131149a7803fada97bb7e36c6174a8f943417ea892e487cd7fdfbf1b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987617/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987617/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29777095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Weirong</creatorcontrib><creatorcontrib>Liu, Jingtian</creatorcontrib><creatorcontrib>Zhang, Dawei</creatorcontrib><creatorcontrib>Huang, Wenhai</creatorcontrib><creatorcontrib>Chen, Runhao</creatorcontrib><title>Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR)</title><title>Medical science monitor</title><addtitle>Med Sci Monit</addtitle><description>BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro. The effect of butein on tumor glycolysis was determined by examining the changes in glucose uptake and lactate production. Hexokinase-2 (HK-2) expression in HCC cells upon butein treatment was analyzed by Western blotting. The activity of butein on EGFR signaling pathway was studied and its potency in EGFR exogenous overexpression cells was investigated. RESULTS After butein treatment, HCC cell proliferation was significantly inhibited (91.4% in Hep3B and 88.2% in Huh-7 at 80 μM, p&lt;0.001). Moreover, the number of colonies formed in the agar was substantially decreased (93.8% in Hep3B and 72.3% in Huh-7 at 80 μM, p&lt;0.001). With the suppression of HK-2 expression, glucose consumption in Hep3B and Huh-7 cells decreased by 48.4% and 56.3%, respectively (p&lt;0.01), and the lactate production also was reduced accordingly (39.5% in Hep3B and 48.6% in Huh-7, p&lt;0.01). Mechanism investigations demonstrated that butein dose-dependently blocked the activation of the EGFR signaling pathway in HCC cells. In EGFR exogenous overexpression cells, the glycolysis suppression exerted by butein was substantially attenuated. CONCLUSIONS Butein has a substantial inhibitory effect on tumor glycolysis in HCC cells, and the glycolysis suppression exerted by butein is closely related to its effect on the EGFR signaling pathway.</description><subject>Apoptosis - drug effects</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chalcones - pharmacology</subject><subject>Glycolysis - drug effects</subject><subject>Hexokinase - metabolism</subject><subject>Humans</subject><subject>Lab/In Vitro Research</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Signal Transduction - drug effects</subject><issn>1643-3750</issn><issn>1234-1010</issn><issn>1643-3750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpVkUtv1DAUhS1ERR-wYo-8LKpS7DiJ7Q0SHc2jUkdIfbC1HOemY3Di1E6A-Rf8ZDxMW5XVPdI5_u6VD0LvKTmneVXKT-ub9bkkVZmLV-iIVgXLGC_J6xf6EB3H-J2QXFSkfIMOc8k5J7I8Qn8uphFsjy_7ja3tCE1S-Jsdg8cr-O1_2F5HyPJsDY3VO_t26nzAS7c13m2jjTg9XsGgR2_AucnpgGc6GNv7TuN6iy-cN4lyj-eDbSB02uFl8L_GDV5oMybUNRgYduJ0vlxcf3yLDlrtIrx7nCfobjG_na2yq6_Ly9mXq8wwQceMgmmZqShllBZSc0FYqxsteV1zYFVyeKFFKwtWUA5ayBwKwU3D26atW1qzE_R5zx2muoPGQD8G7dQQbKfDVnlt1f9Obzfq3v9UpRQ80RPg9BEQ_MMEcVSdjbs_0D34KaqcFLTKS1GJFD3bR03wMQZon9dQov51qFKHat9hSn94edlz9qk09hdSoJnu</recordid><startdate>20180519</startdate><enddate>20180519</enddate><creator>Liao, Weirong</creator><creator>Liu, Jingtian</creator><creator>Zhang, Dawei</creator><creator>Huang, Wenhai</creator><creator>Chen, Runhao</creator><general>International Scientific Literature, Inc</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180519</creationdate><title>Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR)</title><author>Liao, Weirong ; Liu, Jingtian ; Zhang, Dawei ; Huang, Wenhai ; Chen, Runhao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-1ecf3c61131149a7803fada97bb7e36c6174a8f943417ea892e487cd7fdfbf1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Apoptosis - drug effects</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Chalcones - pharmacology</topic><topic>Glycolysis - drug effects</topic><topic>Hexokinase - metabolism</topic><topic>Humans</topic><topic>Lab/In Vitro Research</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Signal Transduction - drug effects</topic><toplevel>online_resources</toplevel><creatorcontrib>Liao, Weirong</creatorcontrib><creatorcontrib>Liu, Jingtian</creatorcontrib><creatorcontrib>Zhang, Dawei</creatorcontrib><creatorcontrib>Huang, Wenhai</creatorcontrib><creatorcontrib>Chen, Runhao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medical science monitor</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Weirong</au><au>Liu, Jingtian</au><au>Zhang, Dawei</au><au>Huang, Wenhai</au><au>Chen, Runhao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR)</atitle><jtitle>Medical science monitor</jtitle><addtitle>Med Sci Monit</addtitle><date>2018-05-19</date><risdate>2018</risdate><volume>24</volume><spage>3283</spage><epage>3292</epage><pages>3283-3292</pages><issn>1643-3750</issn><issn>1234-1010</issn><eissn>1643-3750</eissn><abstract>BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro. The effect of butein on tumor glycolysis was determined by examining the changes in glucose uptake and lactate production. Hexokinase-2 (HK-2) expression in HCC cells upon butein treatment was analyzed by Western blotting. The activity of butein on EGFR signaling pathway was studied and its potency in EGFR exogenous overexpression cells was investigated. RESULTS After butein treatment, HCC cell proliferation was significantly inhibited (91.4% in Hep3B and 88.2% in Huh-7 at 80 μM, p&lt;0.001). Moreover, the number of colonies formed in the agar was substantially decreased (93.8% in Hep3B and 72.3% in Huh-7 at 80 μM, p&lt;0.001). With the suppression of HK-2 expression, glucose consumption in Hep3B and Huh-7 cells decreased by 48.4% and 56.3%, respectively (p&lt;0.01), and the lactate production also was reduced accordingly (39.5% in Hep3B and 48.6% in Huh-7, p&lt;0.01). Mechanism investigations demonstrated that butein dose-dependently blocked the activation of the EGFR signaling pathway in HCC cells. In EGFR exogenous overexpression cells, the glycolysis suppression exerted by butein was substantially attenuated. CONCLUSIONS Butein has a substantial inhibitory effect on tumor glycolysis in HCC cells, and the glycolysis suppression exerted by butein is closely related to its effect on the EGFR signaling pathway.</abstract><cop>United States</cop><pub>International Scientific Literature, Inc</pub><pmid>29777095</pmid><doi>10.12659/MSM.906528</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Apoptosis - drug effects
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Chalcones - pharmacology
Glycolysis - drug effects
Hexokinase - metabolism
Humans
Lab/In Vitro Research
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Receptor, Epidermal Growth Factor - metabolism
Signal Transduction - drug effects
title Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR)
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