Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma
Increasing evidence has indicated that epithelial-to-mesenchymal transition (EMT) at the advanced stage of liver cancer not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radiotherapies. Here, we report that ascochlorin (ASC), a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
American Association for Cancer Research
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/4098 |
| _version_ | 1848744419739566080 |
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| author | Dai, X. Ahn, K. Wang, L. Kim, C. Deivasigamni, A. Arfuso, Frank Um, J. Kumar, Alan Prem Chang, Y. Kumar, D. Kundu, G. Magae, J. Goh, B. Hui, K. Sethi, G. |
| author_facet | Dai, X. Ahn, K. Wang, L. Kim, C. Deivasigamni, A. Arfuso, Frank Um, J. Kumar, Alan Prem Chang, Y. Kumar, D. Kundu, G. Magae, J. Goh, B. Hui, K. Sethi, G. |
| author_sort | Dai, X. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Increasing evidence has indicated that epithelial-to-mesenchymal transition (EMT) at the advanced stage of liver cancer not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radiotherapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic, could potentiate the cytotoxic effect of doxorubicin on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin. Co-administration of ASC reduced doxorubicin-induced invasion/migration and modulated EMT characteristics in mesenchymal cells. This process was probably mediated by the E-cadherin repressors Snail and Slug. In addition, ASC increased sensitivity to doxorubicin treatment by directly inhibiting STAT3 binding to the Snail promoter. We also observed that ASC significantly enhanced the effect of doxorubicin against tumor growth and inhibited metastasis in an HCCLM3-Luc orthotopic mouse model. Collectively, our data demonstrate that ASC can increase sensitivity to doxorubicin therapy and reverse the EMT phenotype via the downregulation of STAT3-Snail expression, which could form the basis of a novel therapeutic approach against hepatocellular carcinoma. |
| first_indexed | 2025-11-14T06:01:10Z |
| format | Journal Article |
| id | curtin-20.500.11937-4098 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:01:10Z |
| publishDate | 2016 |
| publisher | American Association for Cancer Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-40982017-09-13T14:33:01Z Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma Dai, X. Ahn, K. Wang, L. Kim, C. Deivasigamni, A. Arfuso, Frank Um, J. Kumar, Alan Prem Chang, Y. Kumar, D. Kundu, G. Magae, J. Goh, B. Hui, K. Sethi, G. Increasing evidence has indicated that epithelial-to-mesenchymal transition (EMT) at the advanced stage of liver cancer not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radiotherapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic, could potentiate the cytotoxic effect of doxorubicin on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin. Co-administration of ASC reduced doxorubicin-induced invasion/migration and modulated EMT characteristics in mesenchymal cells. This process was probably mediated by the E-cadherin repressors Snail and Slug. In addition, ASC increased sensitivity to doxorubicin treatment by directly inhibiting STAT3 binding to the Snail promoter. We also observed that ASC significantly enhanced the effect of doxorubicin against tumor growth and inhibited metastasis in an HCCLM3-Luc orthotopic mouse model. Collectively, our data demonstrate that ASC can increase sensitivity to doxorubicin therapy and reverse the EMT phenotype via the downregulation of STAT3-Snail expression, which could form the basis of a novel therapeutic approach against hepatocellular carcinoma. 2016 Journal Article http://hdl.handle.net/20.500.11937/4098 10.1158/1535-7163.MCT-16-0391 American Association for Cancer Research restricted |
| spellingShingle | Dai, X. Ahn, K. Wang, L. Kim, C. Deivasigamni, A. Arfuso, Frank Um, J. Kumar, Alan Prem Chang, Y. Kumar, D. Kundu, G. Magae, J. Goh, B. Hui, K. Sethi, G. Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title | Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title_full | Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title_fullStr | Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title_full_unstemmed | Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title_short | Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| title_sort | ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma |
| url | http://hdl.handle.net/20.500.11937/4098 |