Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo
Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, su...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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American Association Cancer Research
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/49793 |
| _version_ | 1848758315871371264 |
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| author | Rajendran, P. Ong, T. Chen, L. Li, F. Shanmugam, M. Vali, S. Abbasi, T. Kapoor, S. Sharma, A. Kumar, Alan Prem Hui, K. Sethi, G. |
| author_facet | Rajendran, P. Ong, T. Chen, L. Li, F. Shanmugam, M. Vali, S. Abbasi, T. Kapoor, S. Sharma, A. Kumar, Alan Prem Hui, K. Sethi, G. |
| author_sort | Rajendran, P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. Thus, the novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. Experimental Design: The effect of butein on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of butein on the growth of human HCC xenograft tumors in male athymic nu/nu mice was also examined. Results: We tested an agent, butein, for its ability to suppress STAT3 activation in HCC cells and nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We found that butein inhibited both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and Janus-activated kinase 2. Butein inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. When administered intraperitoneally, butein inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice. Conclusions: Overall, cumulative results from experimental and predictive studies suggest that butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo. |
| first_indexed | 2025-11-14T09:42:03Z |
| format | Journal Article |
| id | curtin-20.500.11937-49793 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:42:03Z |
| publishDate | 2011 |
| publisher | American Association Cancer Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-497932017-09-13T15:49:25Z Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo Rajendran, P. Ong, T. Chen, L. Li, F. Shanmugam, M. Vali, S. Abbasi, T. Kapoor, S. Sharma, A. Kumar, Alan Prem Hui, K. Sethi, G. Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. Thus, the novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. Experimental Design: The effect of butein on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of butein on the growth of human HCC xenograft tumors in male athymic nu/nu mice was also examined. Results: We tested an agent, butein, for its ability to suppress STAT3 activation in HCC cells and nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We found that butein inhibited both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and Janus-activated kinase 2. Butein inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. When administered intraperitoneally, butein inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice. Conclusions: Overall, cumulative results from experimental and predictive studies suggest that butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo. 2011 Journal Article http://hdl.handle.net/20.500.11937/49793 10.1158/1078-0432.CCR-10-1123 American Association Cancer Research unknown |
| spellingShingle | Rajendran, P. Ong, T. Chen, L. Li, F. Shanmugam, M. Vali, S. Abbasi, T. Kapoor, S. Sharma, A. Kumar, Alan Prem Hui, K. Sethi, G. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title | Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title_full | Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title_fullStr | Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title_full_unstemmed | Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title_short | Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| title_sort | suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo |
| url | http://hdl.handle.net/20.500.11937/49793 |