Recent reports have indicated that
decursin can induce apoptosis, suppress
tumor growth, and inhibit angiogenesis. In this experiment, we investigated how
decursin could potentiate the cytotoxic effects of
bortezomib in human
multiple myeloma cells. We found that
decursin inhibited cell viability in U266, MM.1S and ARH77 cells, but not in peripheral blood mononuclear cells (PBMC).
Decursin-induced apoptosis through the activation of
caspase-8, -9, and -3 in U266 cells. This correlated with the down-regulating of
cyclin D1, bcl-2, bcl-xL,
survivin, and the
vascular endothelial growth factor (
VEGF), which are all regulated by the activation of signal transducers and the activator of transcription 3 (STAT3). Indeed,
decursin inhibited constitutive STAT3 activation through inhibition of the activation of Janus-activated
kinase 2 (JAK2) in U266 cells. In addition,
decursin inhibited interleukin-6-inducible STAT3 activation in a time-dependent manner in MM.1S cells. Interestingly,
decursin significantly potentiated the apoptotic effects of
bortezomib in U266 cells. These effects of
decursin were correlated with the suppression of constitutive STAT3 activation in U266 cells. Overall, these results suggest that
decursin is a novel blocker of STAT3 activation and it may be a potential candidate for overcoming chemo-resistance through suppression of this signaling.