Antineoplastic activity of 2-methoxyestradiol in human pancreatic and gastric cancer cells with different multidrug-resistant phenotypes

J Gastroenterol Hepatol. 2007 Sep;22(9):1469-73. doi: 10.1111/j.1440-1746.2007.05033.x. Epub 2007 Jul 20.

Abstract

Background and aim: Chemoresistance often leads to loss of the last treatment option for cancer. 2-Methoxyestradiol (2-ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2-ME2 on multidrug-resistant human cells from pancreatic and gastric cancer.

Methods: We investigated the impact of 2-ME2 on multidrug-resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1-gene.

Results: In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1-negative and 87% in MDR1-positive cells after 1 micromol/L 2-ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1-positive and 95% in MDR1-negative cells. Strong induction of apoptosis was induced after a low dose of 2-ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug-resistant cells of both tumor types. The number of apoptotic cells after 2-ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1-negative gastric cancer cells.

Conclusion: 2-ME2 may therefore have clinical application for chemoresistant cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Drug Resistance, Multiple*
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Phenotype
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Estradiol
  • 2-Methoxyestradiol