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Selective PKCδ Inhibitor B106 Elicits Uveal Melanoma Growth Inhibitory Effects Independent of Activated PKC Isoforms.

Renier HeijkantsAmina TeunisseJelle de VriesHuib OvaaAart G Jochemsen
Published in: ACS chemical biology (2019)
In uveal melanoma (UM) cells, the protein kinase C (pathway) is almost generally constitutively activated as a result of an activating mutation in either the GNAQ or the GNA11 G-protein. A pan-PKC inhibitor, sotrastaurin (also named AEB071), is in clinical trials for treatment of UM patients with limited success and eliciting adverse effects. Interestingly, genetic interference with expression of just one PKC isoform, e.g., PKCδ, is sufficient to reduce UM cell proliferation. Therefore, we tested the effect of a recently described specific PKCδ inhibitor, B106, on growth and survival of UM cell lines. Surprisingly, we found that B106 efficiently induced apoptosis in several cell lines, but apparently independent of activated PKCδ.
Keyphrases
  • induced apoptosis
  • protein kinase
  • signaling pathway
  • endoplasmic reticulum stress
  • clinical trial
  • cell proliferation
  • oxidative stress
  • cell cycle arrest
  • cell death
  • pi k akt
  • combination therapy
  • open label
  • phase iii