2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-κB signaling by inhibiting Janus kinase 2 and IκB kinase.
Bottom Line: The activation of Janus kinase 2 (JAK2) and IκB kinase (IKK) are key events in STAT3 and NF-κB signaling, respectively.We have identified 2-methoxystypandrone (2-MS) from a traditional Chinese medicinal herb Polygonum cuspidatum as a novel dual inhibitor of JAK2 and IKK. 2-MS inhibits both interleukin-6-induced and constitutively-activated STAT3, as well as tumor necrosis factor-α-induced NF-κB activation. 2-MS specifically inhibits JAK and IKKβ kinase activities but has little effect on activities of other kinases tested.We propose that the natural compound 2-MS, as a potent dual inhibitor of STAT3 and NF-κB pathways, is a promising anticancer drug candidate.
Affiliation: Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.Show MeSH
Related in: MedlinePlus
Mentions: We examined the effects of 2-MS on the NF-κB signaling pathway using an NF-κB responsive luciferase reporter gene-transfected HEK293 cell line. We found that 2-MS inhibited TNF-α-induced NF-κB responsive reporter gene activity in a dose-dependent manner, with a half-maximal inhibition dose of 3 μM (Fig. 4a). Parallel to inhibition of NF-κB signaling, 2-MS only slightly decreased the cell number of HEK293 cells (Fig. 4b), suggesting that the inhibition effect of 2-MS on NF-κB signaling was not caused by reduced cell number.
Affiliation: Division of Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.