Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model
Background Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model. Aim The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibit...
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| creator | Kang, Yong-Hwi Wang, Jing-Hua Lee, Jin-Seok Hwang, Seung-Ju Lee, Nam-Hun Son, Chang-Gue |
| description | Background Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model. Aim The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibits colon-liver metastasis in an animal model, and to elucidate the underlying mechanisms. Methods Murine colon carcinoma (CT26) tumor tissue was implanted into the cecum of balb/c mice with/without oral administration of berberine (100 mg/kg) for 21 days, after which liver metastasis was evaluated. In addition, the pharmacological actions of berberine were explored using 5-fluorouracil-resistant human colon cancer cells (HCT116/R). Result The administration of berberine significantly decreased the number of tumor nodules in the liver, while significant activation of E-cadherin (an epithelial marker), and suppression of vimentin, Snail and TGF-[beta] (mesenchymal markers) were observed in primary colon tumor tissues. Berberine treatment also notably lowered the levels of inflammatory cytokines (TGF-[beta], TNF- [alpha], IL-6 and IL-1[beta]) in the blood. In HCT116/R cells, berberine significantly inhibited migration and invasion and modulated the expression of TGF-[beta] and representative molecules related to its pathway. The results obtained with a TGF-[beta] inhibitor (SB431542) and a TGF-[beta] siRNA, strongly suggest that the mechanism of action of berberine is linked to TGF-[beta] signaling. Conclusion In conclusion, berberine evidently possess an anti-colon-liver metastatic effect, and its underlying mechanisms involve the inhibition of epithelial-mesenchymal transition (EMT) through the TGF-[beta] signaling pathway. Thus, we cautiously propose the pharmacological potential of berberine in drug research studies targeting hepatic metastasis from CRC. Keywords: Colorectal cancer, Metastasis, 5-Fluorouracil, EMT, Berberine, TGF-[beta], Drug resistance |
| doi_str_mv | 10.1186/s40001-024-02122-w |
| format | Article |
| fullrecord | <record><control><sourceid>gale</sourceid><recordid>TN_cdi_gale_infotracmisc_A816684280</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A816684280</galeid><sourcerecordid>A816684280</sourcerecordid><originalsourceid>FETCH-LOGICAL-g980-23ad185072f7f36f23dcd665d5652864b54d4101755d4eb3397841585b5488a93</originalsourceid><addsrcrecordid>eNptkMFKAzEQhnNQsNS-gKeA4G1rkk2y2WMtthUKXnoTKdlkto1kE9ns1tc3RQ8VZGYYmPn-n2EQuqNkTqmSj4kTQmhBGM9FGSu-rtCE1LwuWMnoDZql9JEJIpms6nqCuifoG-hdAOzC0TVuSNhEH3swg_bYuxP0uINBp5wu4ZPTuIt29HpwMeDY4t16Vbw1mXjPDlhjA2bs8NDrkD69DkPGxwRnEfhbdN1qn2D226dot3reLTfF9nX9slxsi0OtSL5UW6oEqVhbtaVsWWmNlVJYIQVTkjeCW04JrYSwHJqyrCvFqVAiL5TSdTlF9z-2B-1h70Ib8zmmc8nsF4pKqThTJFPzf6gcFjpnYoDW5fkfwcOF4AjaD8cU_Xj-RLoEvwEdbnXv</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model</title><source>DOAJ Directory of Open Access Journals</source><source>SpringerNature Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Kang, Yong-Hwi ; Wang, Jing-Hua ; Lee, Jin-Seok ; Hwang, Seung-Ju ; Lee, Nam-Hun ; Son, Chang-Gue</creator><creatorcontrib>Kang, Yong-Hwi ; Wang, Jing-Hua ; Lee, Jin-Seok ; Hwang, Seung-Ju ; Lee, Nam-Hun ; Son, Chang-Gue</creatorcontrib><description>Background Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model. Aim The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibits colon-liver metastasis in an animal model, and to elucidate the underlying mechanisms. Methods Murine colon carcinoma (CT26) tumor tissue was implanted into the cecum of balb/c mice with/without oral administration of berberine (100 mg/kg) for 21 days, after which liver metastasis was evaluated. In addition, the pharmacological actions of berberine were explored using 5-fluorouracil-resistant human colon cancer cells (HCT116/R). Result The administration of berberine significantly decreased the number of tumor nodules in the liver, while significant activation of E-cadherin (an epithelial marker), and suppression of vimentin, Snail and TGF-[beta] (mesenchymal markers) were observed in primary colon tumor tissues. Berberine treatment also notably lowered the levels of inflammatory cytokines (TGF-[beta], TNF- [alpha], IL-6 and IL-1[beta]) in the blood. In HCT116/R cells, berberine significantly inhibited migration and invasion and modulated the expression of TGF-[beta] and representative molecules related to its pathway. The results obtained with a TGF-[beta] inhibitor (SB431542) and a TGF-[beta] siRNA, strongly suggest that the mechanism of action of berberine is linked to TGF-[beta] signaling. Conclusion In conclusion, berberine evidently possess an anti-colon-liver metastatic effect, and its underlying mechanisms involve the inhibition of epithelial-mesenchymal transition (EMT) through the TGF-[beta] signaling pathway. Thus, we cautiously propose the pharmacological potential of berberine in drug research studies targeting hepatic metastasis from CRC. Keywords: Colorectal cancer, Metastasis, 5-Fluorouracil, EMT, Berberine, TGF-[beta], Drug resistance</description><identifier>ISSN: 0949-2321</identifier><identifier>DOI: 10.1186/s40001-024-02122-w</identifier><language>eng</language><publisher>BioMed Central Ltd</publisher><subject>Analysis ; Colon cancer ; Ethylenediaminetetraacetic acid ; Gastrointestinal diseases ; Health aspects ; Liver cancer ; Metastasis ; Scientific equipment and supplies industry ; Stem cells ; Transforming growth factors</subject><ispartof>European journal of medical research, 2024-11, Vol.29 (1)</ispartof><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Kang, Yong-Hwi</creatorcontrib><creatorcontrib>Wang, Jing-Hua</creatorcontrib><creatorcontrib>Lee, Jin-Seok</creatorcontrib><creatorcontrib>Hwang, Seung-Ju</creatorcontrib><creatorcontrib>Lee, Nam-Hun</creatorcontrib><creatorcontrib>Son, Chang-Gue</creatorcontrib><title>Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model</title><title>European journal of medical research</title><description>Background Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model. Aim The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibits colon-liver metastasis in an animal model, and to elucidate the underlying mechanisms. Methods Murine colon carcinoma (CT26) tumor tissue was implanted into the cecum of balb/c mice with/without oral administration of berberine (100 mg/kg) for 21 days, after which liver metastasis was evaluated. In addition, the pharmacological actions of berberine were explored using 5-fluorouracil-resistant human colon cancer cells (HCT116/R). Result The administration of berberine significantly decreased the number of tumor nodules in the liver, while significant activation of E-cadherin (an epithelial marker), and suppression of vimentin, Snail and TGF-[beta] (mesenchymal markers) were observed in primary colon tumor tissues. Berberine treatment also notably lowered the levels of inflammatory cytokines (TGF-[beta], TNF- [alpha], IL-6 and IL-1[beta]) in the blood. In HCT116/R cells, berberine significantly inhibited migration and invasion and modulated the expression of TGF-[beta] and representative molecules related to its pathway. The results obtained with a TGF-[beta] inhibitor (SB431542) and a TGF-[beta] siRNA, strongly suggest that the mechanism of action of berberine is linked to TGF-[beta] signaling. Conclusion In conclusion, berberine evidently possess an anti-colon-liver metastatic effect, and its underlying mechanisms involve the inhibition of epithelial-mesenchymal transition (EMT) through the TGF-[beta] signaling pathway. Thus, we cautiously propose the pharmacological potential of berberine in drug research studies targeting hepatic metastasis from CRC. Keywords: Colorectal cancer, Metastasis, 5-Fluorouracil, EMT, Berberine, TGF-[beta], Drug resistance</description><subject>Analysis</subject><subject>Colon cancer</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Gastrointestinal diseases</subject><subject>Health aspects</subject><subject>Liver cancer</subject><subject>Metastasis</subject><subject>Scientific equipment and supplies industry</subject><subject>Stem cells</subject><subject>Transforming growth factors</subject><issn>0949-2321</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptkMFKAzEQhnNQsNS-gKeA4G1rkk2y2WMtthUKXnoTKdlkto1kE9ns1tc3RQ8VZGYYmPn-n2EQuqNkTqmSj4kTQmhBGM9FGSu-rtCE1LwuWMnoDZql9JEJIpms6nqCuifoG-hdAOzC0TVuSNhEH3swg_bYuxP0uINBp5wu4ZPTuIt29HpwMeDY4t16Vbw1mXjPDlhjA2bs8NDrkD69DkPGxwRnEfhbdN1qn2D226dot3reLTfF9nX9slxsi0OtSL5UW6oEqVhbtaVsWWmNlVJYIQVTkjeCW04JrYSwHJqyrCvFqVAiL5TSdTlF9z-2B-1h70Ib8zmmc8nsF4pKqThTJFPzf6gcFjpnYoDW5fkfwcOF4AjaD8cU_Xj-RLoEvwEdbnXv</recordid><startdate>20241119</startdate><enddate>20241119</enddate><creator>Kang, Yong-Hwi</creator><creator>Wang, Jing-Hua</creator><creator>Lee, Jin-Seok</creator><creator>Hwang, Seung-Ju</creator><creator>Lee, Nam-Hun</creator><creator>Son, Chang-Gue</creator><general>BioMed Central Ltd</general><scope/></search><sort><creationdate>20241119</creationdate><title>Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model</title><author>Kang, Yong-Hwi ; Wang, Jing-Hua ; Lee, Jin-Seok ; Hwang, Seung-Ju ; Lee, Nam-Hun ; Son, Chang-Gue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g980-23ad185072f7f36f23dcd665d5652864b54d4101755d4eb3397841585b5488a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analysis</topic><topic>Colon cancer</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Gastrointestinal diseases</topic><topic>Health aspects</topic><topic>Liver cancer</topic><topic>Metastasis</topic><topic>Scientific equipment and supplies industry</topic><topic>Stem cells</topic><topic>Transforming growth factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Yong-Hwi</creatorcontrib><creatorcontrib>Wang, Jing-Hua</creatorcontrib><creatorcontrib>Lee, Jin-Seok</creatorcontrib><creatorcontrib>Hwang, Seung-Ju</creatorcontrib><creatorcontrib>Lee, Nam-Hun</creatorcontrib><creatorcontrib>Son, Chang-Gue</creatorcontrib><jtitle>European journal of medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Yong-Hwi</au><au>Wang, Jing-Hua</au><au>Lee, Jin-Seok</au><au>Hwang, Seung-Ju</au><au>Lee, Nam-Hun</au><au>Son, Chang-Gue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model</atitle><jtitle>European journal of medical research</jtitle><date>2024-11-19</date><risdate>2024</risdate><volume>29</volume><issue>1</issue><issn>0949-2321</issn><abstract>Background Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model. Aim The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibits colon-liver metastasis in an animal model, and to elucidate the underlying mechanisms. Methods Murine colon carcinoma (CT26) tumor tissue was implanted into the cecum of balb/c mice with/without oral administration of berberine (100 mg/kg) for 21 days, after which liver metastasis was evaluated. In addition, the pharmacological actions of berberine were explored using 5-fluorouracil-resistant human colon cancer cells (HCT116/R). Result The administration of berberine significantly decreased the number of tumor nodules in the liver, while significant activation of E-cadherin (an epithelial marker), and suppression of vimentin, Snail and TGF-[beta] (mesenchymal markers) were observed in primary colon tumor tissues. Berberine treatment also notably lowered the levels of inflammatory cytokines (TGF-[beta], TNF- [alpha], IL-6 and IL-1[beta]) in the blood. In HCT116/R cells, berberine significantly inhibited migration and invasion and modulated the expression of TGF-[beta] and representative molecules related to its pathway. The results obtained with a TGF-[beta] inhibitor (SB431542) and a TGF-[beta] siRNA, strongly suggest that the mechanism of action of berberine is linked to TGF-[beta] signaling. Conclusion In conclusion, berberine evidently possess an anti-colon-liver metastatic effect, and its underlying mechanisms involve the inhibition of epithelial-mesenchymal transition (EMT) through the TGF-[beta] signaling pathway. Thus, we cautiously propose the pharmacological potential of berberine in drug research studies targeting hepatic metastasis from CRC. Keywords: Colorectal cancer, Metastasis, 5-Fluorouracil, EMT, Berberine, TGF-[beta], Drug resistance</abstract><pub>BioMed Central Ltd</pub><doi>10.1186/s40001-024-02122-w</doi></addata></record> |
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| subjects | Analysis Colon cancer Ethylenediaminetetraacetic acid Gastrointestinal diseases Health aspects Liver cancer Metastasis Scientific equipment and supplies industry Stem cells Transforming growth factors |
| title | Berberine inhibits colorectal liver metastasis via modulation of TGF-[beta] in a cecum transplant mouse model |
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