Hydroxyurea promotes TET1 expression and induces apoptosis in osteosarcoma cells

Biosci Rep. 2019 May 14;39(5):BSR20190456. doi: 10.1042/BSR20190456. Print 2019 May 31.

Abstract

Ten-eleven translocation (TET) proteins are abnormally expressed in various cancers. Osteosarcoma cells were treated with hydroxyurea to investigate the expression pattern of TET proteins in these cells. The expression of TET1 was increased in U2OS cells after treatment with hydroxyurea. In addition, hydroxyurea increased cell apoptosis and altered the cell cycle. TET proteins catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC); therefore, 5mC and 5hmC levels were evaluated. Increased 5hmC levels were observed after the hydroxyurea treatment. Experiments examining cell apoptosis and the cell cycle after knockdown and overexpression of TET1 were conducted to further investigate whether TET1 expression affected cell growth. The overexpression of TET1 increased cell apoptosis and inhibited cell growth. Taken together, TET1 expression regulated proliferation and apoptosis in U2OS cells, changes that were associated with 5hmC levels.

Keywords: TET1; cancer; cell apoptosis; cell cycle; hydroxyurea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • 5-Methylcytosine / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Hydroxyurea / pharmacology*
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Up-Regulation / drug effects*

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Mixed Function Oxygenases
  • TET1 protein, human
  • Hydroxyurea