Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances
Chemo-Sensitivity of Cancer Cells to Doxorubicin.
Zhou J, Ong CN, Hur GM, Shen HM.
Department of Epidemiology and Public Health, Yong Loo Lin School of
Medicine, Republic of Korea.
Andrographolide (Andro), a diterpenoid lactone isolated from a
traditional herbal medicine Andrographis paniculata, is known to
possess potent anti-inflammatory and anticancer property. 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
anti-cancer function of Andro and suggest a potential therapeutic
strategy of using Andro in combination with chemotherapeutic agents
for treatment of cancer. Copyright © 2009. Published by Elsevier Inc.
PMID: 20026083 [PubMed - as supplied by publisher]
Posts
