Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital
transcription factor that regulates multiple important biological processes, including the epithelial-mesenchymal transition (EMT) and
metastasis of
breast cancer.
Sinomenine is an
isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several
cancer cell types. Recently,
sinomenine was reported as a
tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of
sinomenine in invasion and
metastasis of
breast cancer are largely unknown. Here, we report that
sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1
breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM
sinomenine. Co-IP analysis revealed that
sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that
sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB
kinase (IKK) and its negative regulator CUEDC2.
Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and
metastasis of MDA-MB-231 and 4T1 cell by
sinomenine, providing evidence that
sinomenine treatment suppressed
breast cancer cell invasion and
metastasis via regulation of the
IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which
sinomenine suppresses
cancer cell invasion and
metastasis, i.e., blocking NF-κB activation.