Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling

Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed th...

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Veröffentlicht in:Molecular medicine reports 2018-10, Vol.18 (4), p.4030-4036
Hauptverfasser: Zhao, Xuezhi, Guo, Xiaohan, Shen, Junhua, Hua, Dingchao
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Guo, Xiaohan
Shen, Junhua
Hua, Dingchao
description Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit‑8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X protein, cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), cyclin D1, cyclin‑dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)‑STAT3, c‑myc, survivin, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose‑ and time‑dependent manner, and cells were arrested in the G1 phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase‑3 and PARP, and downregulated protein expression levels of Bcl‑2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP‑1 and TIMP‑2, and decreased protein expression levels of MMP‑2 and MMP‑9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p‑STAT3 and reduced expression of downstream factors, including c‑myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.
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Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit‑8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X protein, cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), cyclin D1, cyclin‑dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)‑STAT3, c‑myc, survivin, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose‑ and time‑dependent manner, and cells were arrested in the G1 phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase‑3 and PARP, and downregulated protein expression levels of Bcl‑2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP‑1 and TIMP‑2, and decreased protein expression levels of MMP‑2 and MMP‑9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p‑STAT3 and reduced expression of downstream factors, including c‑myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2018.9420</identifier><identifier>PMID: 30132572</identifier><language>eng</language><publisher>Greece: Spandidos Publications UK Ltd</publisher><subject>Anti-inflammatory agents ; Antineoplastic Agents, Phytogenic - chemistry ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; B-cell lymphoma ; Bax protein ; Bcl-2 protein ; Biotechnology ; c-Myc protein ; Cancer therapies ; Caspase ; Caspase-3 ; Cell adhesion &amp; migration ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Chemotherapy ; Colonies ; Cyclin D1 ; Cyclin-dependent kinase 4 ; Cyclin-dependent kinases ; Female ; Flavanones - chemistry ; Flavanones - pharmacology ; Flow cytometry ; G1 phase ; G1 Phase - drug effects ; Gelatinase A ; Humans ; Immunoglobulins ; Inflammation ; Kinases ; Lung cancer ; Lymphocytes B ; Matrix Metalloproteinases - metabolism ; Metastasis ; Ovarian cancer ; Ovarian Neoplasms - enzymology ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Poly(ADP-ribose) polymerase ; Protein expression ; Proteins ; S Phase - drug effects ; Signal transduction ; Signal Transduction - drug effects ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - metabolism ; Spheroids, Cellular - pathology ; STAT3 Transcription Factor - metabolism ; Studies ; Tissue Inhibitor of Metalloproteinases ; Transcription ; Tumor Stem Cell Assay ; Tumorigenesis ; Wound healing</subject><ispartof>Molecular medicine reports, 2018-10, Vol.18 (4), p.4030-4036</ispartof><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-83e69c1b7bcc0e2ebd53152ba7a376436d096fbcbf763517f55713cabfaa72f83</citedby><cites>FETCH-LOGICAL-c360t-83e69c1b7bcc0e2ebd53152ba7a376436d096fbcbf763517f55713cabfaa72f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30132572$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Xuezhi</creatorcontrib><creatorcontrib>Guo, Xiaohan</creatorcontrib><creatorcontrib>Shen, Junhua</creatorcontrib><creatorcontrib>Hua, Dingchao</creatorcontrib><title>Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit‑8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X protein, cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), cyclin D1, cyclin‑dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)‑STAT3, c‑myc, survivin, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose‑ and time‑dependent manner, and cells were arrested in the G1 phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase‑3 and PARP, and downregulated protein expression levels of Bcl‑2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP‑1 and TIMP‑2, and decreased protein expression levels of MMP‑2 and MMP‑9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p‑STAT3 and reduced expression of downstream factors, including c‑myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.</description><subject>Anti-inflammatory agents</subject><subject>Antineoplastic Agents, Phytogenic - chemistry</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>B-cell lymphoma</subject><subject>Bax protein</subject><subject>Bcl-2 protein</subject><subject>Biotechnology</subject><subject>c-Myc protein</subject><subject>Cancer therapies</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Colonies</subject><subject>Cyclin D1</subject><subject>Cyclin-dependent kinase 4</subject><subject>Cyclin-dependent kinases</subject><subject>Female</subject><subject>Flavanones - chemistry</subject><subject>Flavanones - pharmacology</subject><subject>Flow cytometry</subject><subject>G1 phase</subject><subject>G1 Phase - drug effects</subject><subject>Gelatinase A</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lymphocytes B</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Metastasis</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - enzymology</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>S Phase - drug effects</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Spheroids, Cellular - pathology</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Studies</subject><subject>Tissue Inhibitor of Metalloproteinases</subject><subject>Transcription</subject><subject>Tumor Stem Cell Assay</subject><subject>Tumorigenesis</subject><subject>Wound healing</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkTtPwzAUhS0EolAYWZElFpYUP-o4HquKl1SJgTJHtmMXV4kT7KQS_x5HDQxM917p09G55wBwg9GCFoI8NE1YEISLhVgSdAIuMBc4owgtT6edCMFn4DLGPUI5I0ycgxlFmBLGyQVwq7pz3vTOQ-c_nXJ9hF1oa2dNkL1rPZS-go3bTVdrYXuQwUkPtfTaBKhNXUd4cBLGoeuCiXHi3rerLYXR7bysnd9dgTMr62iupzkHH0-P2_VLtnl7fl2vNpmmOeqzgppcaKy40hoZYlTFKGZESS4pz5c0r5DIrdLK8pwyzC1jHFMtlZWSE1vQObg_6qY3vgYT-7JxcTQpvWmHWBIkcIEZEyihd__QfTuEZDdRGAmU0ipworIjpUMbYzC27IJrZPguMSrHDsrUQTl2UI4dJP52Uh1UY6o_-jd0-gOLR4MZ</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Zhao, Xuezhi</creator><creator>Guo, Xiaohan</creator><creator>Shen, Junhua</creator><creator>Hua, Dingchao</creator><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</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>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20181001</creationdate><title>Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling</title><author>Zhao, Xuezhi ; Guo, Xiaohan ; Shen, Junhua ; Hua, Dingchao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-83e69c1b7bcc0e2ebd53152ba7a376436d096fbcbf763517f55713cabfaa72f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anti-inflammatory agents</topic><topic>Antineoplastic Agents, Phytogenic - chemistry</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>B-cell lymphoma</topic><topic>Bax protein</topic><topic>Bcl-2 protein</topic><topic>Biotechnology</topic><topic>c-Myc protein</topic><topic>Cancer therapies</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell adhesion &amp; migration</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chemotherapy</topic><topic>Colonies</topic><topic>Cyclin D1</topic><topic>Cyclin-dependent kinase 4</topic><topic>Cyclin-dependent kinases</topic><topic>Female</topic><topic>Flavanones - chemistry</topic><topic>Flavanones - pharmacology</topic><topic>Flow cytometry</topic><topic>G1 phase</topic><topic>G1 Phase - drug effects</topic><topic>Gelatinase A</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lymphocytes B</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Metastasis</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - enzymology</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>S Phase - drug effects</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Spheroids, Cellular - pathology</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Studies</topic><topic>Tissue Inhibitor of Metalloproteinases</topic><topic>Transcription</topic><topic>Tumor Stem Cell Assay</topic><topic>Tumorigenesis</topic><topic>Wound healing</topic><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Xuezhi</creatorcontrib><creatorcontrib>Guo, Xiaohan</creatorcontrib><creatorcontrib>Shen, Junhua</creatorcontrib><creatorcontrib>Hua, Dingchao</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>Health &amp; 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Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit‑8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X protein, cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), cyclin D1, cyclin‑dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)‑STAT3, c‑myc, survivin, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose‑ and time‑dependent manner, and cells were arrested in the G1 phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase‑3 and PARP, and downregulated protein expression levels of Bcl‑2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP‑1 and TIMP‑2, and decreased protein expression levels of MMP‑2 and MMP‑9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p‑STAT3 and reduced expression of downstream factors, including c‑myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.</abstract><cop>Greece</cop><pub>Spandidos Publications UK Ltd</pub><pmid>30132572</pmid><doi>10.3892/mmr.2018.9420</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Anti-inflammatory agents
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis
Apoptosis - drug effects
B-cell lymphoma
Bax protein
Bcl-2 protein
Biotechnology
c-Myc protein
Cancer therapies
Caspase
Caspase-3
Cell adhesion & migration
Cell cycle
Cell Cycle Proteins - metabolism
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell proliferation
Cell Proliferation - drug effects
Cell Survival - drug effects
Chemotherapy
Colonies
Cyclin D1
Cyclin-dependent kinase 4
Cyclin-dependent kinases
Female
Flavanones - chemistry
Flavanones - pharmacology
Flow cytometry
G1 phase
G1 Phase - drug effects
Gelatinase A
Humans
Immunoglobulins
Inflammation
Kinases
Lung cancer
Lymphocytes B
Matrix Metalloproteinases - metabolism
Metastasis
Ovarian cancer
Ovarian Neoplasms - enzymology
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Poly(ADP-ribose) polymerase
Protein expression
Proteins
S Phase - drug effects
Signal transduction
Signal Transduction - drug effects
Spheroids, Cellular - drug effects
Spheroids, Cellular - metabolism
Spheroids, Cellular - pathology
STAT3 Transcription Factor - metabolism
Studies
Tissue Inhibitor of Metalloproteinases
Transcription
Tumor Stem Cell Assay
Tumorigenesis
Wound healing
title Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling
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