Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway
Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we...
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creator | JIN, HANA LEE, WON SUP EUN, SO YOUNG JUNG, JI HYUN PARK, HYEON-SOO KIM, GONSUP CHOI, YUNG HYUN RYU, CHUNG HO JUNG, JIN MYUNG HONG, SOON CHAN SHIN, SUNG CHUL KIM, HYE JUNG |
description | Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB-231 breast cancer cells from low doses (50 μM) without cytotoxicity. In addition, morin changed MDA-MB-231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB-231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB-231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB-231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB-231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer. |
doi_str_mv | 10.3892/ijo.2014.2535 |
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However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB-231 breast cancer cells from low doses (50 μM) without cytotoxicity. In addition, morin changed MDA-MB-231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB-231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB-231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB-231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB-231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2014.2535</identifier><identifier>PMID: 24993541</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Akt pathway ; Animals ; Antineoplastic Agents - pharmacology ; Bioflavonoids ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Care and treatment ; Cell culture ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cellular signal transduction ; Control ; Cytotoxicity ; Epithelial-Mesenchymal Transition - drug effects ; Female ; Flavones ; Flavonoids ; Flavonoids - pharmacology ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genetic aspects ; Health aspects ; Humans ; invasion ; MAP Kinase Signaling System - drug effects ; Membranes ; Metastasis ; Mice ; Mice, Nude ; Moraceae - chemistry ; morin ; N-cadherin ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Penicillin ; Phosphorylation ; Physiological aspects ; Plant Extracts - pharmacology ; Studies ; Tumor necrosis factor-TNF ; Xenograft Model Antitumor Assays</subject><ispartof>International journal of oncology, 2014-10, Vol.45 (4), p.1629-1637</ispartof><rights>Copyright © 2014, Spandidos Publications</rights><rights>COPYRIGHT 2014 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-26b02644bdad8cba0618269b6f33c0594d519c012477da471b9a0e1b1658b5ef3</citedby><cites>FETCH-LOGICAL-c556t-26b02644bdad8cba0618269b6f33c0594d519c012477da471b9a0e1b1658b5ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,5556,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24993541$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JIN, HANA</creatorcontrib><creatorcontrib>LEE, WON SUP</creatorcontrib><creatorcontrib>EUN, SO YOUNG</creatorcontrib><creatorcontrib>JUNG, JI HYUN</creatorcontrib><creatorcontrib>PARK, HYEON-SOO</creatorcontrib><creatorcontrib>KIM, GONSUP</creatorcontrib><creatorcontrib>CHOI, YUNG HYUN</creatorcontrib><creatorcontrib>RYU, CHUNG HO</creatorcontrib><creatorcontrib>JUNG, JIN MYUNG</creatorcontrib><creatorcontrib>HONG, SOON CHAN</creatorcontrib><creatorcontrib>SHIN, SUNG CHUL</creatorcontrib><creatorcontrib>KIM, HYE JUNG</creatorcontrib><title>Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB-231 breast cancer cells from low doses (50 μM) without cytotoxicity. In addition, morin changed MDA-MB-231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB-231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB-231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB-231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB-231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.</description><subject>Akt pathway</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Bioflavonoids</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular signal transduction</subject><subject>Control</subject><subject>Cytotoxicity</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Female</subject><subject>Flavones</subject><subject>Flavonoids</subject><subject>Flavonoids - pharmacology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>invasion</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Membranes</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Moraceae - chemistry</subject><subject>morin</subject><subject>N-cadherin</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Penicillin</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Plant Extracts - pharmacology</subject><subject>Studies</subject><subject>Tumor necrosis factor-TNF</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkktv1DAUhSMEoqWwZIssIcGmHvxOvBzKU-qIDawtx3EmHhI72E6r-Uv8SjyaMrQS8sJXV985V74-VfUSoxVtJHnndmFFEGYrwil_VJ3jWmJIGKGPS42whIJReVY9S2mHEOEc4afVGWFSUs7wefV7E6Lzl0CDftQ3wQfXgT6GCZS-NlbbS5CWeY42JZvANobbPADtO-D8jU4ueBB6kAcLBrcdxj2YbNYp6-wMaKMtJTDaGxuBseMIRuct2HxYw817SCgGs465iPIQw7IdTpPu2a5_5kLl4Vbvn1dPej0m--Luvqh-fPr4_eoLvP72-evV-hoazkWGRLSICMbaTneNaTUSuCFCtqKn1CAuWcexNAgTVtedZjVupUYWt1jwpuW2pxfV66PvHMOvxaasdmGJvoxUWFJCKcNC_KO2erTK-T7ksrDJJaPWtOGoxrRuCrX6D1VOZydngre9K_0Hgjf3BIPVYx5SGJdcdpIegvAImhhSirZXc3STjnuFkTokQ5VkqEMy1CEZhX9196qlnWx3ov9GoQBvj0Cay_-6LqQTU5wg4xAxiAWR9A_My7_8</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>JIN, HANA</creator><creator>LEE, WON SUP</creator><creator>EUN, SO YOUNG</creator><creator>JUNG, JI HYUN</creator><creator>PARK, HYEON-SOO</creator><creator>KIM, GONSUP</creator><creator>CHOI, YUNG HYUN</creator><creator>RYU, CHUNG HO</creator><creator>JUNG, JIN MYUNG</creator><creator>HONG, SOON CHAN</creator><creator>SHIN, SUNG CHUL</creator><creator>KIM, HYE JUNG</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20141001</creationdate><title>Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway</title><author>JIN, HANA ; LEE, WON SUP ; EUN, SO YOUNG ; JUNG, JI HYUN ; PARK, HYEON-SOO ; KIM, GONSUP ; CHOI, YUNG HYUN ; RYU, CHUNG HO ; JUNG, JIN MYUNG ; HONG, SOON CHAN ; SHIN, SUNG CHUL ; KIM, HYE JUNG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-26b02644bdad8cba0618269b6f33c0594d519c012477da471b9a0e1b1658b5ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Akt pathway</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Bioflavonoids</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Care and treatment</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cellular signal transduction</topic><topic>Control</topic><topic>Cytotoxicity</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Female</topic><topic>Flavones</topic><topic>Flavonoids</topic><topic>Flavonoids - pharmacology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>invasion</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Membranes</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Moraceae - chemistry</topic><topic>morin</topic><topic>N-cadherin</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Penicillin</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Plant Extracts - pharmacology</topic><topic>Studies</topic><topic>Tumor necrosis factor-TNF</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JIN, HANA</creatorcontrib><creatorcontrib>LEE, WON SUP</creatorcontrib><creatorcontrib>EUN, SO YOUNG</creatorcontrib><creatorcontrib>JUNG, JI HYUN</creatorcontrib><creatorcontrib>PARK, HYEON-SOO</creatorcontrib><creatorcontrib>KIM, GONSUP</creatorcontrib><creatorcontrib>CHOI, YUNG HYUN</creatorcontrib><creatorcontrib>RYU, CHUNG HO</creatorcontrib><creatorcontrib>JUNG, JIN MYUNG</creatorcontrib><creatorcontrib>HONG, SOON CHAN</creatorcontrib><creatorcontrib>SHIN, SUNG CHUL</creatorcontrib><creatorcontrib>KIM, HYE JUNG</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>ProQuest Nursing and Allied Health Journals</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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 China</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JIN, HANA</au><au>LEE, WON SUP</au><au>EUN, SO YOUNG</au><au>JUNG, JI HYUN</au><au>PARK, HYEON-SOO</au><au>KIM, GONSUP</au><au>CHOI, YUNG HYUN</au><au>RYU, CHUNG HO</au><au>JUNG, JIN MYUNG</au><au>HONG, SOON CHAN</au><au>SHIN, SUNG CHUL</au><au>KIM, HYE JUNG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>45</volume><issue>4</issue><spage>1629</spage><epage>1637</epage><pages>1629-1637</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB-231 breast cancer cells from low doses (50 μM) without cytotoxicity. In addition, morin changed MDA-MB-231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB-231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB-231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB-231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB-231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>24993541</pmid><doi>10.3892/ijo.2014.2535</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Akt pathway Animals Antineoplastic Agents - pharmacology Bioflavonoids Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Care and treatment Cell culture Cell Line, Tumor Cell Proliferation - drug effects Cellular signal transduction Control Cytotoxicity Epithelial-Mesenchymal Transition - drug effects Female Flavones Flavonoids Flavonoids - pharmacology Gene expression Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Health aspects Humans invasion MAP Kinase Signaling System - drug effects Membranes Metastasis Mice Mice, Nude Moraceae - chemistry morin N-cadherin Neoplasm Invasiveness Neoplasm Metastasis Penicillin Phosphorylation Physiological aspects Plant Extracts - pharmacology Studies Tumor necrosis factor-TNF Xenograft Model Antitumor Assays |
title | Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway |
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