Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer
Purpose Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemopreven...
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| Veröffentlicht in: | European journal of nutrition 2016-04, Vol.55 (3), p.955-965 |
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| creator | Kubatka, Peter Kapinová, Andrea Kello, Martin Kruzliak, Peter Kajo, Karol Výbohová, Desanka Mahmood, Silvia Murin, Radovan Viera, Tischlerová Mojžiš, Ján Zulli, Anthony Péč, Martin Adamkov, Marián Kassayová, Monika Bojková, Bianka Stollárová, Nadežda Dobrota, Dušan |
| description | Purpose
Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of
N
-methyl-
N
-nitrosourea-induced mammary carcinogenesis in female rats were evaluated.
Methods
Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed.
Results
High-dose F7 suppressed tumour frequency by 58 % (
P
|
| doi_str_mv | 10.1007/s00394-015-0910-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1777836496</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4008248831</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-94e8c7b96bc4c8b4bdac8ee43b78d8794cc0e66cddf9612d024d7cfd135ee0013</originalsourceid><addsrcrecordid>eNp1kD1PwzAQhi0EolD4ASzIEnPgHDt2PKKKAlIlFphNYl9oqnxhO0P_PalaKhamO-nej9NDyA2DewagHgIA1yIBliWgGSTZCblggstEpiw7Pe6gZuQyhA0ApFyyczJLM81By-yCfC79WEc6IDZ06JvtsMaubwJ12PZdiL6ISMNYhlh0sS4auhtJHNt-9BSrCm0MtO5oXCNtezeF9BUtPRYhUlt0Fv0VOauKJuD1Yc7Jx_LpffGSrN6eXxePq8RylcZEC8ytKrUsrbB5KUpX2BxR8FLlLldaWAsopXWu0pKlDlLhlK0c4xkiAONzcrfPHXz_PWKIZjP92E2Vhimlci6FlpOK7VXW9yF4rMzg67bwW8PA7JiaPVMzMTU7piabPLeH5LFs0R0dvxAnQboXhOnUfaH_U_1v6g8szINw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1777836496</pqid></control><display><type>article</type><title>Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Kubatka, Peter ; Kapinová, Andrea ; Kello, Martin ; Kruzliak, Peter ; Kajo, Karol ; Výbohová, Desanka ; Mahmood, Silvia ; Murin, Radovan ; Viera, Tischlerová ; Mojžiš, Ján ; Zulli, Anthony ; Péč, Martin ; Adamkov, Marián ; Kassayová, Monika ; Bojková, Bianka ; Stollárová, Nadežda ; Dobrota, Dušan</creator><creatorcontrib>Kubatka, Peter ; Kapinová, Andrea ; Kello, Martin ; Kruzliak, Peter ; Kajo, Karol ; Výbohová, Desanka ; Mahmood, Silvia ; Murin, Radovan ; Viera, Tischlerová ; Mojžiš, Ján ; Zulli, Anthony ; Péč, Martin ; Adamkov, Marián ; Kassayová, Monika ; Bojková, Bianka ; Stollárová, Nadežda ; Dobrota, Dušan</creatorcontrib><description>Purpose
Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of
N
-methyl-
N
-nitrosourea-induced mammary carcinogenesis in female rats were evaluated.
Methods
Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed.
Results
High-dose F7 suppressed tumour frequency by 58 % (
P
< 0.001), tumour incidence by 24 % (
P
< 0.05), and lengthened latency by 8 days (
P
> 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation.
Conclusions
Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.</description><identifier>ISSN: 1436-6207</identifier><identifier>EISSN: 1436-6215</identifier><identifier>DOI: 10.1007/s00394-015-0910-5</identifier><identifier>PMID: 25930965</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - analysis ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis - drug effects ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Cell Proliferation - drug effects ; Chemistry ; Chemistry and Materials Science ; Disease Models, Animal ; DNA Fragmentation - drug effects ; Dose-Response Relationship, Drug ; Female ; Flavonoids - analysis ; Flavonoids - pharmacology ; Fruit - chemistry ; Humans ; Ki-67 Antigen - genetics ; Ki-67 Antigen - metabolism ; Mammary Neoplasms, Experimental - drug therapy ; MCF-7 Cells ; Methylnitrosourea - toxicity ; Nutrition ; Original Contribution ; Polyphenols - analysis ; Polyphenols - pharmacology ; Rats ; Stilbenes - analysis ; Stilbenes - pharmacology ; Tyrosine - analogs & derivatives ; Tyrosine - metabolism ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><ispartof>European journal of nutrition, 2016-04, Vol.55 (3), p.955-965</ispartof><rights>Springer-Verlag Berlin Heidelberg 2015</rights><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-94e8c7b96bc4c8b4bdac8ee43b78d8794cc0e66cddf9612d024d7cfd135ee0013</citedby><cites>FETCH-LOGICAL-c372t-94e8c7b96bc4c8b4bdac8ee43b78d8794cc0e66cddf9612d024d7cfd135ee0013</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/s00394-015-0910-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00394-015-0910-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25930965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubatka, Peter</creatorcontrib><creatorcontrib>Kapinová, Andrea</creatorcontrib><creatorcontrib>Kello, Martin</creatorcontrib><creatorcontrib>Kruzliak, Peter</creatorcontrib><creatorcontrib>Kajo, Karol</creatorcontrib><creatorcontrib>Výbohová, Desanka</creatorcontrib><creatorcontrib>Mahmood, Silvia</creatorcontrib><creatorcontrib>Murin, Radovan</creatorcontrib><creatorcontrib>Viera, Tischlerová</creatorcontrib><creatorcontrib>Mojžiš, Ján</creatorcontrib><creatorcontrib>Zulli, Anthony</creatorcontrib><creatorcontrib>Péč, Martin</creatorcontrib><creatorcontrib>Adamkov, Marián</creatorcontrib><creatorcontrib>Kassayová, Monika</creatorcontrib><creatorcontrib>Bojková, Bianka</creatorcontrib><creatorcontrib>Stollárová, Nadežda</creatorcontrib><creatorcontrib>Dobrota, Dušan</creatorcontrib><title>Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer</title><title>European journal of nutrition</title><addtitle>Eur J Nutr</addtitle><addtitle>Eur J Nutr</addtitle><description>Purpose
Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of
N
-methyl-
N
-nitrosourea-induced mammary carcinogenesis in female rats were evaluated.
Methods
Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed.
Results
High-dose F7 suppressed tumour frequency by 58 % (
P
< 0.001), tumour incidence by 24 % (
P
< 0.05), and lengthened latency by 8 days (
P
> 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation.
Conclusions
Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - analysis</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Disease Models, Animal</subject><subject>DNA Fragmentation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Flavonoids - analysis</subject><subject>Flavonoids - pharmacology</subject><subject>Fruit - chemistry</subject><subject>Humans</subject><subject>Ki-67 Antigen - genetics</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Mammary Neoplasms, Experimental - drug therapy</subject><subject>MCF-7 Cells</subject><subject>Methylnitrosourea - toxicity</subject><subject>Nutrition</subject><subject>Original Contribution</subject><subject>Polyphenols - analysis</subject><subject>Polyphenols - pharmacology</subject><subject>Rats</subject><subject>Stilbenes - analysis</subject><subject>Stilbenes - pharmacology</subject><subject>Tyrosine - analogs & derivatives</subject><subject>Tyrosine - metabolism</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><issn>1436-6207</issn><issn>1436-6215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kD1PwzAQhi0EolD4ASzIEnPgHDt2PKKKAlIlFphNYl9oqnxhO0P_PalaKhamO-nej9NDyA2DewagHgIA1yIBliWgGSTZCblggstEpiw7Pe6gZuQyhA0ApFyyczJLM81By-yCfC79WEc6IDZ06JvtsMaubwJ12PZdiL6ISMNYhlh0sS4auhtJHNt-9BSrCm0MtO5oXCNtezeF9BUtPRYhUlt0Fv0VOauKJuD1Yc7Jx_LpffGSrN6eXxePq8RylcZEC8ytKrUsrbB5KUpX2BxR8FLlLldaWAsopXWu0pKlDlLhlK0c4xkiAONzcrfPHXz_PWKIZjP92E2Vhimlci6FlpOK7VXW9yF4rMzg67bwW8PA7JiaPVMzMTU7piabPLeH5LFs0R0dvxAnQboXhOnUfaH_U_1v6g8szINw</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Kubatka, Peter</creator><creator>Kapinová, Andrea</creator><creator>Kello, Martin</creator><creator>Kruzliak, Peter</creator><creator>Kajo, Karol</creator><creator>Výbohová, Desanka</creator><creator>Mahmood, Silvia</creator><creator>Murin, Radovan</creator><creator>Viera, Tischlerová</creator><creator>Mojžiš, Ján</creator><creator>Zulli, Anthony</creator><creator>Péč, Martin</creator><creator>Adamkov, Marián</creator><creator>Kassayová, Monika</creator><creator>Bojková, Bianka</creator><creator>Stollárová, Nadežda</creator><creator>Dobrota, Dušan</creator><general>Springer Berlin Heidelberg</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>7QP</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20160401</creationdate><title>Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer</title><author>Kubatka, Peter ; Kapinová, Andrea ; Kello, Martin ; Kruzliak, Peter ; Kajo, Karol ; Výbohová, Desanka ; Mahmood, Silvia ; Murin, Radovan ; Viera, Tischlerová ; Mojžiš, Ján ; Zulli, Anthony ; Péč, Martin ; Adamkov, Marián ; Kassayová, Monika ; Bojková, Bianka ; Stollárová, Nadežda ; Dobrota, Dušan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-94e8c7b96bc4c8b4bdac8ee43b78d8794cc0e66cddf9612d024d7cfd135ee0013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - analysis</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Caspase 3 - genetics</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Disease Models, Animal</topic><topic>DNA Fragmentation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Flavonoids - analysis</topic><topic>Flavonoids - pharmacology</topic><topic>Fruit - chemistry</topic><topic>Humans</topic><topic>Ki-67 Antigen - genetics</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Mammary Neoplasms, Experimental - drug therapy</topic><topic>MCF-7 Cells</topic><topic>Methylnitrosourea - toxicity</topic><topic>Nutrition</topic><topic>Original Contribution</topic><topic>Polyphenols - analysis</topic><topic>Polyphenols - pharmacology</topic><topic>Rats</topic><topic>Stilbenes - analysis</topic><topic>Stilbenes - pharmacology</topic><topic>Tyrosine - analogs & derivatives</topic><topic>Tyrosine - metabolism</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubatka, Peter</creatorcontrib><creatorcontrib>Kapinová, Andrea</creatorcontrib><creatorcontrib>Kello, Martin</creatorcontrib><creatorcontrib>Kruzliak, Peter</creatorcontrib><creatorcontrib>Kajo, Karol</creatorcontrib><creatorcontrib>Výbohová, Desanka</creatorcontrib><creatorcontrib>Mahmood, Silvia</creatorcontrib><creatorcontrib>Murin, Radovan</creatorcontrib><creatorcontrib>Viera, Tischlerová</creatorcontrib><creatorcontrib>Mojžiš, Ján</creatorcontrib><creatorcontrib>Zulli, Anthony</creatorcontrib><creatorcontrib>Péč, Martin</creatorcontrib><creatorcontrib>Adamkov, Marián</creatorcontrib><creatorcontrib>Kassayová, Monika</creatorcontrib><creatorcontrib>Bojková, Bianka</creatorcontrib><creatorcontrib>Stollárová, Nadežda</creatorcontrib><creatorcontrib>Dobrota, Dušan</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>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Career and Technical Education</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</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><jtitle>European journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubatka, Peter</au><au>Kapinová, Andrea</au><au>Kello, Martin</au><au>Kruzliak, Peter</au><au>Kajo, Karol</au><au>Výbohová, Desanka</au><au>Mahmood, Silvia</au><au>Murin, Radovan</au><au>Viera, Tischlerová</au><au>Mojžiš, Ján</au><au>Zulli, Anthony</au><au>Péč, Martin</au><au>Adamkov, Marián</au><au>Kassayová, Monika</au><au>Bojková, Bianka</au><au>Stollárová, Nadežda</au><au>Dobrota, Dušan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer</atitle><jtitle>European journal of nutrition</jtitle><stitle>Eur J Nutr</stitle><addtitle>Eur J Nutr</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>55</volume><issue>3</issue><spage>955</spage><epage>965</epage><pages>955-965</pages><issn>1436-6207</issn><eissn>1436-6215</eissn><abstract>Purpose
Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of
N
-methyl-
N
-nitrosourea-induced mammary carcinogenesis in female rats were evaluated.
Methods
Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed.
Results
High-dose F7 suppressed tumour frequency by 58 % (
P
< 0.001), tumour incidence by 24 % (
P
< 0.05), and lengthened latency by 8 days (
P
> 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation.
Conclusions
Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>25930965</pmid><doi>10.1007/s00394-015-0910-5</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| subjects | Animals Antineoplastic Agents, Phytogenic - analysis Antineoplastic Agents, Phytogenic - pharmacology Apoptosis - drug effects bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Caspase 3 - genetics Caspase 3 - metabolism Cell Proliferation - drug effects Chemistry Chemistry and Materials Science Disease Models, Animal DNA Fragmentation - drug effects Dose-Response Relationship, Drug Female Flavonoids - analysis Flavonoids - pharmacology Fruit - chemistry Humans Ki-67 Antigen - genetics Ki-67 Antigen - metabolism Mammary Neoplasms, Experimental - drug therapy MCF-7 Cells Methylnitrosourea - toxicity Nutrition Original Contribution Polyphenols - analysis Polyphenols - pharmacology Rats Stilbenes - analysis Stilbenes - pharmacology Tyrosine - analogs & derivatives Tyrosine - metabolism Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer |
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