Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma.
Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression an...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3589458?pdf=render |
| _version_ | 1819103964321284096 |
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| author | Kanjoormana Aryan Manu Muthu K Shanmugam Tina H Ong Aruljothi Subramaniam Kodappully Sivaraman Siveen Ekambaram Perumal Ramar Perumal Samy Pradeep Bist Lina H K Lim Alan Prem Kumar Kam M Hui Gautam Sethi |
| author_facet | Kanjoormana Aryan Manu Muthu K Shanmugam Tina H Ong Aruljothi Subramaniam Kodappully Sivaraman Siveen Ekambaram Perumal Ramar Perumal Samy Pradeep Bist Lina H K Lim Alan Prem Kumar Kam M Hui Gautam Sethi |
| author_sort | Kanjoormana Aryan Manu |
| collection | DOAJ |
| description | Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC. |
| first_indexed | 2024-12-22T01:58:49Z |
| format | Article |
| id | doaj.art-9406d97962e542f680431496d85ca9dd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:58:49Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9406d97962e542f680431496d85ca9dd2022-12-21T18:42:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5701510.1371/journal.pone.0057015Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma.Kanjoormana Aryan ManuMuthu K ShanmugamTina H OngAruljothi SubramaniamKodappully Sivaraman SiveenEkambaram PerumalRamar Perumal SamyPradeep BistLina H K LimAlan Prem KumarKam M HuiGautam SethiAccumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC.http://europepmc.org/articles/PMC3589458?pdf=render |
| spellingShingle | Kanjoormana Aryan Manu Muthu K Shanmugam Tina H Ong Aruljothi Subramaniam Kodappully Sivaraman Siveen Ekambaram Perumal Ramar Perumal Samy Pradeep Bist Lina H K Lim Alan Prem Kumar Kam M Hui Gautam Sethi Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS ONE |
| title | Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. |
| title_full | Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. |
| title_fullStr | Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. |
| title_full_unstemmed | Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. |
| title_short | Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. |
| title_sort | emodin suppresses migration and invasion through the modulation of cxcr4 expression in an orthotopic model of human hepatocellular carcinoma |
| url | http://europepmc.org/articles/PMC3589458?pdf=render |
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