Biochem Biophys Res Commun 2007,
PMID: 17585881
Miyatake, Katsutoshi; Inoue, Hiroshi; Hashimoto, Kahoko; Takaku, Hiroshi; Takata, Yoichiro; Nakano, Shunji; Yasui, Natsuo; Itakura, Mitsuo
PKC412 (CGP41251) is a multitarget protein kinase inhibitor with anti-tumor activities. Here, we investigated the effects of PKC412 on macrophages. PKC412 inhibited the proliferation of murine RAW 264.7 macrophages through induction of G2/M cell cycle arrest and apoptosis. At non-toxic drug concentrations, PKC412 significantly suppressed the lipopolysaccharide (LPS)-induced release of TNF-alpha and nitric oxide, while instead enhancing IL-6 secretion. PKC412 attenuated LPS-induced phosphorylations of MKK4 and JNK, as well as AP-1 DNA binding activities. Furthermore, PKC412 suppressed LPS-induced Akt and GSK-3beta phosphorylations. These results suggest that the anti-proliferative and immunomodulatory effects of PKC412 are, at least in part, mediated through its interference with the MKK4/JNK/AP-1 and/or Akt/GSK-3beta pathways. Since macrophages contribute significantly to the development of both acute and chronic inflammation, PKC412 may have therapeutic potential and applications in treating inflammatory and/or autoimmune diseases.
Document information provided by NCBI PubMed
Text Mining Data
TNF-alpha → lipopolysaccharide (LPS): "
At non-toxic drug concentrations, PKC412 significantly suppressed the
lipopolysaccharide (LPS) induced release of
TNF-alpha and nitric oxide, while instead enhancing IL-6 secretion
"
Akt → LPS: "
Furthermore, PKC412 suppressed LPS induced Akt and GSK-3beta phosphorylations
"
GSK-3beta → LPS: "
Furthermore, PKC412 suppressed LPS induced Akt and GSK-3beta phosphorylations
"
Manually curated Databases
No curated data.