Hydroxyurea Induces a Senescence-Like Change of K562 Human Erythroleukemia Cell

J Cancer Res Clin Oncol. 2000 Aug;126(8):455-60.

Abstract

Hydroxyurea, a differentiation-inducing agent of human erythroleukemia K562 cells, is commonly used to treat some types of leukemia. However, the mechanism for its therapeutic effect is not clearly understood yet. In this study, we have observed an interesting effect of hydroxyurea on tumor cells: an induction of senescence-like changes. Human erythroleukemia K562 cells, when treated with hydroxyurea for 7 days or more, underwent a change into phenotypically senescent cells together with a reduction of hemoglobin generation, a differentiation marker. The hydroxyurea-treated cells showed positive senescence associated-beta-galactosidase staining, a senescence index, and the accumulation of cdk (cyclin dependent kinase) inhibitors, such as p16INK4a, p21Waf1, and p27Kip1, implicated in cellular senescence. Nonetheless, these changes were not accompanied by DNA fragmentation. Taken together, we summarize that the long-term treatment of cancer cells with hydroxyurea can induce cellular senescence different from differentiation or programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • DNA, Neoplasm / analysis
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydroxyurea / pharmacology*
  • Hydroxyurea / therapeutic use
  • K562 Cells / drug effects*
  • K562 Cells / pathology
  • Leukemia, Erythroblastic, Acute / drug therapy*
  • beta-Galactosidase / analysis

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Cyclin-Dependent Kinases
  • beta-Galactosidase
  • Hydroxyurea