Yessotoxin activates cell death pathways independent of Protein Kinase C in K-562 human leukemic cell line

Toxicol In Vitro. 2015 Oct;29(7):1545-54. doi: 10.1016/j.tiv.2015.05.013. Epub 2015 May 27.


Protein Kinase C (PKC) is a group of enzymes involved in pro-survival or pro-apoptotic events depending on the cellular model. Moreover, Yessotoxin (YTX) modulates its expression and activates different cell death pathways. In K-562 tumor cell line, YTX induces apoptosis and autophagy after 24 and 48 h of incubation, respectively, and the toxin carries out its action through the phosphodiesterase 4A (PDE4A). Therefore, the levels of two subtypes of PKC, conventional (cPKC) and δ isotype of novel PKC (PKCδ) were studied at these times after YTX incubation. Also their involvement in the cell death activated by the toxin and their relationship with PDE4A was checked. The expression of cPKC and PKCδ in cytosol, plasma membrane and nucleus was studied in normal and PDE4A-silenced cells. Furthermore, cell viability of normal cells, as well as cPKC-, PKCδ- and PDE4A-silenced cells was tested by Lactate Dehydrogenase (LDH) assay. As a result, PKCδ showed a key role in K-562 cell survive, since without this protein, K-562 cell decreased their viability. Furthermore, modulation of PKCs by YTX treatment was observed, however, the changes in the expression of these proteins are independent of cell death activated by the toxin. In addition, the modulation of PKCs detected is PDE4A-dependent, since the silencing of this protein change PKC expression pattern.

Keywords: PDE4A; PKC delta; Viability; YTX; cPKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Cytosol / metabolism
  • Humans
  • Isoenzymes / metabolism
  • K562 Cells
  • Leukemia / metabolism
  • Oxocins / pharmacology*
  • Protein Kinase C / metabolism*


  • Isoenzymes
  • Oxocins
  • Protein Kinase C
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4A protein, human
  • yessotoxin