Effects of azidothymidine on protein kinase C activity and expression in erythroleukemic cell K562 and acute lymphoblastic leukemia cell HSB-2

Acta Biochim Biophys Sin (Shanghai). 2015 Apr;47(4):278-84. doi: 10.1093/abbs/gmv003. Epub 2015 Feb 18.

Abstract

Azidothymidine (AZT) is one of the anti-retroviral drugs currently used for the treatment of HIV-infected patients. Several other effects of the drug have been studied in vitro, such as the alterations of some enzymes, the inhibition of cell proliferation, and the increase of transferrin receptor expression. In this study, we investigated the alterations of protein kinase C (PKC) activity, PKCα and PKCβII expressions and plasmatic membrane fluidity induced by AZT in two cancer cell lines, human chronic myeloid (K562) and human acute lymphoblastic (HSB-2) leukemia cells, respectively. The results showed that both PKC activity and membrane fluidity in HSB-2 cells increased after 24 h of drug incubation. PKCα expression in HSB-2 cells decreased after 48 h of AZT exposure, when the cell growth also decreased. However, in K562 cells, the PKCα and PKCβII expressions enhanced in the presence of the drug when the growth was inhibited. The results indicate that AZT is less effective in inhibiting the growth of acute lymphoblastic HSB-2 leukemia cells than inhibiting that of chronic myeloid K562 cells. In fact, after 24 h exposure, the HSB-2 cell growth decreased less than K562 cell growth.

Keywords: AZT; HSB-2 cell; K562 cell; PKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Immunoblotting
  • K562 Cells
  • Leukemia, Erythroblastic, Acute / enzymology
  • Leukemia, Erythroblastic, Acute / pathology
  • Membrane Fluidity / drug effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Protein Kinase C beta / metabolism*
  • Protein Kinase C-alpha / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Zidovudine / pharmacology*

Substances

  • Anti-HIV Agents
  • Zidovudine
  • PRKCA protein, human
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Tetradecanoylphorbol Acetate