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Article: Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma
Title | Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma |
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Authors | |
Keywords | Animal experiment Cancer cell culture Cell invasion Cell migration Cell motility |
Issue Date | 2012 |
Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
Citation | PLoS One, 2012, v. 7 n. 9, article no. e46318 How to Cite? |
Abstract | AIM OF THE STUDY: Hepatocellular carcinoma is one of the most malignant human cancers with high metastatic potential. The aim of this study is to investigate the anti-metastatic effect of genipin and its underlying mechanism. EXPERIMENTAL APPROACH: The anti-metastatic potential of genipin was evaluated by both cell and animal model. Wound healing and invasion chamber assays were introduced to examine the anti-migration and anti-invasion action of genipin in human hepatocellular carcinoma cell HepG2 and MHCC97L; orthotopical implantation model was used for in vivo evaluation. Gelatin Zymography, Immunoblotting, quantitative real-time polymerase chain reaction and ELISA assays were used to study the mechanisms underlying genipin's anti-metastatic effect. KEY RESULTS: Genipin suppresses the motility and invasiveness of HepG2 and MHCC97L at non-toxic doses, which may be correlated to the inhibition of genipin on MMP-2 activities in the cells. No significant reduced expression of MMP-2 was observed either at mRNA or at protein level. Furthermore, genipin could specifically up-regulate the expression of TIMP-1, the endogenous inhibitor of MMP-2 activities. Silencing of TIMP-1 by RNA interference abolishes genipin's anti-metastaic effect. Activation of p38 MAPK signaling was observed in genipin-treated cells, which is responsible for the TIMP-1 overexpression and MMP-2 inhibition. Presence of SB202190, the p38 MAPK inhibitor, attenuates the anti-metastatic potential of genipin in hepatocellular carcinoma. Orthotopical implantation model showed that genipin could suppress the intrahepatic metastatic as well as tumor expansion in liver without exhibiting potent toxicity. CONCLUSION: Our findings demonstrated the potential of genipin in suppressing hepatocellular carcinoma metastasis, and p38/TIMP-1/MMP-2 pathway may be involved as the key mechanism of its anti-metastasis effect. |
Persistent Identifier | http://hdl.handle.net/10722/169170 |
ISSN | 2023 Impact Factor: 2.9 2023 SCImago Journal Rankings: 0.839 |
PubMed Central ID | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, N | en_HK |
dc.contributor.author | Zhu, M | en_HK |
dc.contributor.author | Tsao, SW | en_HK |
dc.contributor.author | Man, K | en_HK |
dc.contributor.author | Zhang, Z | en_HK |
dc.contributor.author | Feng, Y | en_HK |
dc.date.accessioned | 2012-10-18T08:45:07Z | - |
dc.date.available | 2012-10-18T08:45:07Z | - |
dc.date.issued | 2012 | en_HK |
dc.identifier.citation | PLoS One, 2012, v. 7 n. 9, article no. e46318 | en_HK |
dc.identifier.issn | 1932-6203 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/169170 | - |
dc.description.abstract | AIM OF THE STUDY: Hepatocellular carcinoma is one of the most malignant human cancers with high metastatic potential. The aim of this study is to investigate the anti-metastatic effect of genipin and its underlying mechanism. EXPERIMENTAL APPROACH: The anti-metastatic potential of genipin was evaluated by both cell and animal model. Wound healing and invasion chamber assays were introduced to examine the anti-migration and anti-invasion action of genipin in human hepatocellular carcinoma cell HepG2 and MHCC97L; orthotopical implantation model was used for in vivo evaluation. Gelatin Zymography, Immunoblotting, quantitative real-time polymerase chain reaction and ELISA assays were used to study the mechanisms underlying genipin's anti-metastatic effect. KEY RESULTS: Genipin suppresses the motility and invasiveness of HepG2 and MHCC97L at non-toxic doses, which may be correlated to the inhibition of genipin on MMP-2 activities in the cells. No significant reduced expression of MMP-2 was observed either at mRNA or at protein level. Furthermore, genipin could specifically up-regulate the expression of TIMP-1, the endogenous inhibitor of MMP-2 activities. Silencing of TIMP-1 by RNA interference abolishes genipin's anti-metastaic effect. Activation of p38 MAPK signaling was observed in genipin-treated cells, which is responsible for the TIMP-1 overexpression and MMP-2 inhibition. Presence of SB202190, the p38 MAPK inhibitor, attenuates the anti-metastatic potential of genipin in hepatocellular carcinoma. Orthotopical implantation model showed that genipin could suppress the intrahepatic metastatic as well as tumor expansion in liver without exhibiting potent toxicity. CONCLUSION: Our findings demonstrated the potential of genipin in suppressing hepatocellular carcinoma metastasis, and p38/TIMP-1/MMP-2 pathway may be involved as the key mechanism of its anti-metastasis effect. | en_HK |
dc.language | eng | en_US |
dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | en_HK |
dc.relation.ispartof | PLoS ONE | en_HK |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Animal experiment | - |
dc.subject | Cancer cell culture | - |
dc.subject | Cell invasion | - |
dc.subject | Cell migration | - |
dc.subject | Cell motility | - |
dc.title | Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Wang, N: ckwang@hku.hk | en_HK |
dc.identifier.email | Zhu, M: mfzhu@hku.hk | en_HK |
dc.identifier.email | Tsao, SW: gswtsao@hku.hk | en_HK |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.email | Zhang, Z: zhangzj@hkucc.hku.hk | - |
dc.identifier.email | Feng, Y: yfeng@hku.hk | - |
dc.identifier.authority | Man, K=rp00417 | en_HK |
dc.identifier.authority | Zhang, Z=rp01297 | en_HK |
dc.identifier.authority | Feng, Y=rp00466 | en_HK |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1371/journal.pone.0046318 | en_HK |
dc.identifier.pmid | 23029478 | - |
dc.identifier.pmcid | PMC3461024 | - |
dc.identifier.scopus | eid_2-s2.0-84867000366 | en_HK |
dc.identifier.hkuros | 216751 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-84867000366&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 7 | en_HK |
dc.identifier.issue | 9, article no. e46318 | en_HK |
dc.identifier.isi | WOS:000309973900133 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Feng, Y=24467969600 | en_HK |
dc.identifier.scopusauthorid | Zhang, Z=8061473900 | en_HK |
dc.identifier.scopusauthorid | Man, K=7101754072 | en_HK |
dc.identifier.scopusauthorid | Tsao, SW=55311525100 | en_HK |
dc.identifier.scopusauthorid | Zhu, M=36706949300 | en_HK |
dc.identifier.scopusauthorid | Wang, N=55359687200 | en_HK |
dc.identifier.issnl | 1932-6203 | - |