Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bcp.2009.12.014
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dc.titleInhibition of the JAK-STAT3 pathway by andrographolide enhances chemosensitivity of cancer cells to doxorubicin
dc.contributor.authorZhou, J.
dc.contributor.authorOng, C.-N.
dc.contributor.authorShen, H.-M.
dc.contributor.authorHur, G.-M.
dc.date.accessioned2011-07-26T02:52:08Z
dc.date.available2011-07-26T02:52:08Z
dc.date.issued2010
dc.identifier.citationZhou, J., Ong, C.-N., Shen, H.-M., Hur, G.-M. (2010). Inhibition of the JAK-STAT3 pathway by andrographolide enhances chemosensitivity of cancer cells to doxorubicin. Biochemical Pharmacology 79 (9) : 1242-1250. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bcp.2009.12.014
dc.identifier.issn00062952
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/24575
dc.description.abstractAndrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess potent anti-inflammatory and anticancer properties. In this study, we sought to examine the effect of Andro on signal transducer and activator of transcription 3 (STAT3) pathway and evaluate whether suppression of STAT3 activity by Andro could sensitize cancer cells to a chemotherapeutic drug doxorubicin. First, we demonstrated that Andro is able to significantly suppress both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through suppression of Janus-activated kinase (JAK)1/2 and interaction between STAT3 and gp130. For understanding the biological significance of the inhibitory effect of Andro on STAT3, we next investigated the effect of Andro on doxorubicin-induced apoptosis in human cancer cells. In our study the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to doxorubicin-induced apoptosis. Both the short-term MTT assay and the long-term colony formation assay showed that Andro dramatically promoted doxorubicin-induced cell death in cancer cells, indicating that Andro enhances the sensitivity of cancer cells to doxorubicin mainly via STAT3 suppression. These observations thus reveal a novel anticancer function of Andro and suggest a potential therapeutic strategy of using Andro in combination with chemotherapeutic agents for treatment of cancer. © 2009 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.bcp.2009.12.014
dc.sourceScopus
dc.subjectAndro
dc.subjectApoptosis
dc.subjectDoxorubicin
dc.subjectSTAT3
dc.typeArticle
dc.contributor.departmentEPIDEMIOLOGY & PUBLIC HEALTH
dc.description.doi10.1016/j.bcp.2009.12.014
dc.description.sourcetitleBiochemical Pharmacology
dc.description.volume79
dc.description.issue9
dc.description.page1242-1250
dc.identifier.isiut000275681900004
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