Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma
•Grape seeds (GSE) and grape skin (GSK) intake inhibited tumor growth in mice.•GSE + GSK induced cell cycle arrest and markedly decreased cancer cell proliferation.•GSE + GSK profoundly induced apoptosis via the mitochondrial pathway.•GSE + GSK represents a potent chemopreventive agent against the g...
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| Veröffentlicht in: | Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2019-02, Vol.58, p.100-109 |
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| creator | Badr El-Din, Nariman K. Ali, Doaa A. Abou-El-Magd, Rania F. |
| description | •Grape seeds (GSE) and grape skin (GSK) intake inhibited tumor growth in mice.•GSE + GSK induced cell cycle arrest and markedly decreased cancer cell proliferation.•GSE + GSK profoundly induced apoptosis via the mitochondrial pathway.•GSE + GSK represents a potent chemopreventive agent against the growth of tumors.
Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms.
GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated.
GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression.
The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors. |
| doi_str_mv | 10.1016/j.nut.2018.06.018 |
| format | Article |
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Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms.
GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated.
GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression.
The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.</description><identifier>ISSN: 0899-9007</identifier><identifier>EISSN: 1873-1244</identifier><identifier>DOI: 10.1016/j.nut.2018.06.018</identifier><identifier>PMID: 30391688</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anticancer properties ; Anticarcinogenic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Ascites ; B-cell lymphoma ; Cancer therapies ; Carcinoma, Ehrlich Tumor - drug therapy ; Caspase ; Caspase-3 ; Cell cycle ; Cell growth ; Cell proliferation ; Chemoprevention ; Clinical trials ; Diet ; Disease Models, Animal ; Electron microscopy ; Experiments ; Female ; Flow cytometry ; G1 phase ; G1 Phase - drug effects ; Grape seeds ; Grape skin ; Grapes ; Inoculation ; Laboratory animals ; Lymphocytes B ; Lymphoma ; Malignancy ; Mice ; Mortality ; p53 Protein ; Phytochemicals ; Plant Extracts - pharmacology ; Proteins ; Seeds ; Skin ; Solid tumors ; Tumor cells ; Tumors ; Vitis ; Weight reduction</subject><ispartof>Nutrition (Burbank, Los Angeles County, Calif.), 2019-02, Vol.58, p.100-109</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-77f2df407325c3ff43cf5eb0cffe10dbb1af3fdc0f1d7b9a93ba485b8889f77b3</citedby><cites>FETCH-LOGICAL-c381t-77f2df407325c3ff43cf5eb0cffe10dbb1af3fdc0f1d7b9a93ba485b8889f77b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2166088622?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30391688$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Badr El-Din, Nariman K.</creatorcontrib><creatorcontrib>Ali, Doaa A.</creatorcontrib><creatorcontrib>Abou-El-Magd, Rania F.</creatorcontrib><title>Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma</title><title>Nutrition (Burbank, Los Angeles County, Calif.)</title><addtitle>Nutrition</addtitle><description>•Grape seeds (GSE) and grape skin (GSK) intake inhibited tumor growth in mice.•GSE + GSK induced cell cycle arrest and markedly decreased cancer cell proliferation.•GSE + GSK profoundly induced apoptosis via the mitochondrial pathway.•GSE + GSK represents a potent chemopreventive agent against the growth of tumors.
Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms.
GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated.
GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression.
The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.</description><subject>Animals</subject><subject>Anticancer properties</subject><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Ascites</subject><subject>B-cell lymphoma</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ehrlich Tumor - drug therapy</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Chemoprevention</subject><subject>Clinical trials</subject><subject>Diet</subject><subject>Disease Models, Animal</subject><subject>Electron microscopy</subject><subject>Experiments</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>G1 phase</subject><subject>G1 Phase - drug effects</subject><subject>Grape seeds</subject><subject>Grape skin</subject><subject>Grapes</subject><subject>Inoculation</subject><subject>Laboratory animals</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Malignancy</subject><subject>Mice</subject><subject>Mortality</subject><subject>p53 Protein</subject><subject>Phytochemicals</subject><subject>Plant Extracts - pharmacology</subject><subject>Proteins</subject><subject>Seeds</subject><subject>Skin</subject><subject>Solid tumors</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vitis</subject><subject>Weight reduction</subject><issn>0899-9007</issn><issn>1873-1244</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1u1TAUhC0EopeWB2CDLLFhk3Ac58cRK1SVW6RK3dC15djHxJckDrbTiifoa-NySxcsuhrp6JvR6Awh7xiUDFj76VAuWyorYKKEtszyguyY6HjBqrp-SXYg-r7oAboT8ibGAwCwvu1fkxMOvGetEDtyvw9qRRoRTaRqMTT-dAt1i9k00rTNPtAfwd-lMd9GN7jk_EJvnaJ7VqyjikhVCBjTX69a_Zp8dDHDdHY5wS1eb5NKaOidyyEXY5icHqmK2iWMVKugMzOrM_LKqini20c9JTdfL76fXxZX1_tv51-uCs0FS0XX2crYGjpeNZpbW3NtGxxAW4sMzDAwZbk1Giwz3dCrng-qFs0ghOht1w38lHw85q7B_9pycTm7qHGa1IJ-i7JiHKARTS0y-uE_9OC3sOR2mWpbEKKtqkyxI6WDjzGglWtwswq_JQP5sJI8yLySfFhJQiuzZM_7x-RtmNE8Of7NkoHPRwDzK24dBpn_hYtG4wLqJI13z8T_Ac6ppSw</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Badr El-Din, Nariman K.</creator><creator>Ali, Doaa A.</creator><creator>Abou-El-Magd, Rania F.</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>201902</creationdate><title>Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma</title><author>Badr El-Din, Nariman K. ; Ali, Doaa A. ; Abou-El-Magd, Rania F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-77f2df407325c3ff43cf5eb0cffe10dbb1af3fdc0f1d7b9a93ba485b8889f77b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Anticancer properties</topic><topic>Anticarcinogenic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Ascites</topic><topic>B-cell lymphoma</topic><topic>Cancer therapies</topic><topic>Carcinoma, Ehrlich Tumor - drug therapy</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Chemoprevention</topic><topic>Clinical trials</topic><topic>Diet</topic><topic>Disease Models, Animal</topic><topic>Electron microscopy</topic><topic>Experiments</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>G1 phase</topic><topic>G1 Phase - drug effects</topic><topic>Grape seeds</topic><topic>Grape skin</topic><topic>Grapes</topic><topic>Inoculation</topic><topic>Laboratory animals</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Malignancy</topic><topic>Mice</topic><topic>Mortality</topic><topic>p53 Protein</topic><topic>Phytochemicals</topic><topic>Plant Extracts - pharmacology</topic><topic>Proteins</topic><topic>Seeds</topic><topic>Skin</topic><topic>Solid tumors</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Vitis</topic><topic>Weight reduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Badr El-Din, Nariman K.</creatorcontrib><creatorcontrib>Ali, Doaa A.</creatorcontrib><creatorcontrib>Abou-El-Magd, Rania F.</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>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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 Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Badr El-Din, Nariman K.</au><au>Ali, Doaa A.</au><au>Abou-El-Magd, Rania F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma</atitle><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle><addtitle>Nutrition</addtitle><date>2019-02</date><risdate>2019</risdate><volume>58</volume><spage>100</spage><epage>109</epage><pages>100-109</pages><issn>0899-9007</issn><eissn>1873-1244</eissn><abstract>•Grape seeds (GSE) and grape skin (GSK) intake inhibited tumor growth in mice.•GSE + GSK induced cell cycle arrest and markedly decreased cancer cell proliferation.•GSE + GSK profoundly induced apoptosis via the mitochondrial pathway.•GSE + GSK represents a potent chemopreventive agent against the growth of tumors.
Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms.
GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated.
GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression.
The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30391688</pmid><doi>10.1016/j.nut.2018.06.018</doi><tpages>10</tpages></addata></record> |
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| issn | 0899-9007 1873-1244 |
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| subjects | Animals Anticancer properties Anticarcinogenic Agents - pharmacology Apoptosis Apoptosis - drug effects Ascites B-cell lymphoma Cancer therapies Carcinoma, Ehrlich Tumor - drug therapy Caspase Caspase-3 Cell cycle Cell growth Cell proliferation Chemoprevention Clinical trials Diet Disease Models, Animal Electron microscopy Experiments Female Flow cytometry G1 phase G1 Phase - drug effects Grape seeds Grape skin Grapes Inoculation Laboratory animals Lymphocytes B Lymphoma Malignancy Mice Mortality p53 Protein Phytochemicals Plant Extracts - pharmacology Proteins Seeds Skin Solid tumors Tumor cells Tumors Vitis Weight reduction |
| title | Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma |
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