Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP‐9 and Akt signaling
Metastasis is the most prevalent cause of cancer‐related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the ant...
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| Veröffentlicht in: | Environmental toxicology 2021-10, Vol.36 (10), p.1981-1989 |
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| container_end_page | 1989 |
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| container_issue | 10 |
| container_start_page | 1981 |
| container_title | Environmental toxicology |
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| creator | Ju, Po‐Chung Ho, Yung‐Chuan Chen, Pei‐Ni Lee, Hsiang‐Lin Lai, Szu‐Yu Yang, Shun‐Fa Yeh, Chao‐Bin |
| description | Metastasis is the most prevalent cause of cancer‐related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti‐invasive and anti‐migratory effects of kaempferol on human HCC cells. The anti‐invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh‐7 and SK‐Hep‐1). Kaempferol reduced the invasion and migration of Huh‐7 and SK‐Hep‐1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase‐9 (MMP‐9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP‐9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP‐9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells. |
| doi_str_mv | 10.1002/tox.23316 |
| format | Article |
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Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti‐invasive and anti‐migratory effects of kaempferol on human HCC cells. The anti‐invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh‐7 and SK‐Hep‐1). Kaempferol reduced the invasion and migration of Huh‐7 and SK‐Hep‐1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase‐9 (MMP‐9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP‐9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP‐9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.23316</identifier><identifier>PMID: 34156145</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>AKT protein ; Anticancer properties ; Assaying ; Boyden chamber ; Cancer ; Carcinoma, Hepatocellular - drug therapy ; Cell Line ; Cell Line, Tumor ; Cell lines ; Cell migration ; Cell Movement ; Cells ; Chemical compounds ; Flavonoids ; Flavonols ; Gelatin ; HCC ; Hepatocellular carcinoma ; Humans ; Invasiveness ; Kaempferol ; Kaempferols - pharmacology ; Liver cancer ; Liver Neoplasms - drug therapy ; Matrix metalloproteinase ; Matrix Metalloproteinase 9 - genetics ; Matrix Metalloproteinase 9 - metabolism ; Matrix metalloproteinases ; Metalloproteinase ; Metastases ; migration ; MMP‐9 ; Neoplasm Invasiveness ; Neoplasms ; Pharmacology ; Phosphorylation ; Proto-Oncogene Proteins c-akt - genetics ; Subgroups ; Wound healing</subject><ispartof>Environmental toxicology, 2021-10, Vol.36 (10), p.1981-1989</ispartof><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3536-fd2f82d9706841a3d12a066123cb9cd9d6eecf506e28eefdf9630e7f5b204b143</citedby><cites>FETCH-LOGICAL-c3536-fd2f82d9706841a3d12a066123cb9cd9d6eecf506e28eefdf9630e7f5b204b143</cites><orcidid>0000-0002-0365-7927</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.23316$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.23316$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34156145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ju, Po‐Chung</creatorcontrib><creatorcontrib>Ho, Yung‐Chuan</creatorcontrib><creatorcontrib>Chen, Pei‐Ni</creatorcontrib><creatorcontrib>Lee, Hsiang‐Lin</creatorcontrib><creatorcontrib>Lai, Szu‐Yu</creatorcontrib><creatorcontrib>Yang, Shun‐Fa</creatorcontrib><creatorcontrib>Yeh, Chao‐Bin</creatorcontrib><title>Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP‐9 and Akt signaling</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Metastasis is the most prevalent cause of cancer‐related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti‐invasive and anti‐migratory effects of kaempferol on human HCC cells. The anti‐invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh‐7 and SK‐Hep‐1). Kaempferol reduced the invasion and migration of Huh‐7 and SK‐Hep‐1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase‐9 (MMP‐9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP‐9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP‐9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells.</description><subject>AKT protein</subject><subject>Anticancer properties</subject><subject>Assaying</subject><subject>Boyden chamber</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cells</subject><subject>Chemical compounds</subject><subject>Flavonoids</subject><subject>Flavonols</subject><subject>Gelatin</subject><subject>HCC</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Kaempferol</subject><subject>Kaempferols - pharmacology</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Metalloproteinase</subject><subject>Metastases</subject><subject>migration</subject><subject>MMP‐9</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasms</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Subgroups</subject><subject>Wound healing</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kbtOwzAUhi0EglIYeAFkiQWGgC-Jk4wV4iaoylAktshJjltDEgc7EXTjEXhGngS3BQYkJls63_l09P8IHVBySglhZ515O2WcU7GBBjRiLIhZnGyu_iQISUJ30K5zT4SQVERiG-3wkEaChtEAvd5KqFsF1lRYN3Od687hbg64gKrCtZ5Z2WnTYKPwvK9lg-fQys4sp30lLS6kLXRjarlacDhfYNe3rQXndDPD4_H95_tHimVT4tFzh52eNbLykz20pWTlYP_7HaKHy4vp-XVwN7m6OR_dBQWPuAhUyVTCyjQmIgmp5CVlkghBGS_ytCjTUgAUKiICWAKgSpUKTiBWUc5ImNOQD9Hx2tta89KD67Jau-WpsgHTu4xFoc8i9ll49OgP-mR6689dUiLxQiJiT52sqcIa5yyorLW6lnaRUZIt28h8G9mqDc8efhv7vIbyl_yJ3wNna-BVV7D435RNJ49r5ReJtpWc</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Ju, Po‐Chung</creator><creator>Ho, Yung‐Chuan</creator><creator>Chen, Pei‐Ni</creator><creator>Lee, Hsiang‐Lin</creator><creator>Lai, Szu‐Yu</creator><creator>Yang, Shun‐Fa</creator><creator>Yeh, Chao‐Bin</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, 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>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid></search><sort><creationdate>202110</creationdate><title>Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP‐9 and Akt signaling</title><author>Ju, Po‐Chung ; Ho, Yung‐Chuan ; Chen, Pei‐Ni ; Lee, Hsiang‐Lin ; Lai, Szu‐Yu ; Yang, Shun‐Fa ; Yeh, Chao‐Bin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3536-fd2f82d9706841a3d12a066123cb9cd9d6eecf506e28eefdf9630e7f5b204b143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>AKT protein</topic><topic>Anticancer properties</topic><topic>Assaying</topic><topic>Boyden chamber</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cells</topic><topic>Chemical compounds</topic><topic>Flavonoids</topic><topic>Flavonols</topic><topic>Gelatin</topic><topic>HCC</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Kaempferol</topic><topic>Kaempferols - pharmacology</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Metalloproteinase</topic><topic>Metastases</topic><topic>migration</topic><topic>MMP‐9</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasms</topic><topic>Pharmacology</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Subgroups</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ju, Po‐Chung</creatorcontrib><creatorcontrib>Ho, Yung‐Chuan</creatorcontrib><creatorcontrib>Chen, Pei‐Ni</creatorcontrib><creatorcontrib>Lee, Hsiang‐Lin</creatorcontrib><creatorcontrib>Lai, Szu‐Yu</creatorcontrib><creatorcontrib>Yang, Shun‐Fa</creatorcontrib><creatorcontrib>Yeh, Chao‐Bin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ju, Po‐Chung</au><au>Ho, Yung‐Chuan</au><au>Chen, Pei‐Ni</au><au>Lee, Hsiang‐Lin</au><au>Lai, Szu‐Yu</au><au>Yang, Shun‐Fa</au><au>Yeh, Chao‐Bin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP‐9 and Akt signaling</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2021-10</date><risdate>2021</risdate><volume>36</volume><issue>10</issue><spage>1981</spage><epage>1989</epage><pages>1981-1989</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Metastasis is the most prevalent cause of cancer‐related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti‐invasive and anti‐migratory effects of kaempferol on human HCC cells. The anti‐invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh‐7 and SK‐Hep‐1). Kaempferol reduced the invasion and migration of Huh‐7 and SK‐Hep‐1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase‐9 (MMP‐9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP‐9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP‐9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>34156145</pmid><doi>10.1002/tox.23316</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0365-7927</orcidid></addata></record> |
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| subjects | AKT protein Anticancer properties Assaying Boyden chamber Cancer Carcinoma, Hepatocellular - drug therapy Cell Line Cell Line, Tumor Cell lines Cell migration Cell Movement Cells Chemical compounds Flavonoids Flavonols Gelatin HCC Hepatocellular carcinoma Humans Invasiveness Kaempferol Kaempferols - pharmacology Liver cancer Liver Neoplasms - drug therapy Matrix metalloproteinase Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Matrix metalloproteinases Metalloproteinase Metastases migration MMP‐9 Neoplasm Invasiveness Neoplasms Pharmacology Phosphorylation Proto-Oncogene Proteins c-akt - genetics Subgroups Wound healing |
| title | Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP‐9 and Akt signaling |
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