Concentration- and time-dependent effects of enoxaparin on human adenocarcinomic epithelial cell line A549 proliferation in vitro

Can J Physiol Pharmacol. 2011 Oct;89(10):705-11. doi: 10.1139/y11-068. Epub 2011 Sep 9.

Abstract

Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only potential curative treatment, in spite of the high recurrence and mortality rates. Low molecular weight heparins (LMWH) have been suggested to have a positive impact on the outcome of various cancers, mainly attributed to their anticoagulant properties; yet a direct antineoplastic effect has not been excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the human lung adenocarcinomic epithelial cell line A549 and to determine potential antiproliferative and antimetastatic effects that could guide future trials. A549 cells were cultured with different concentrations of enoxaparin (1-30 U/mL). Cell counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44 protein was performed by electrophoresis and Western blotting. Statistical analysis was performed using paired Student's t tests. Cell counts were decreased with increasing concentrations and time of exposure to enoxaparin. This corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin displayed a direct dose and exposure duration dependent suppressor effect on A549 cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting reduced proliferative and metastatic potentials of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • Enoxaparin / pharmacology
  • Enoxaparin / therapeutic use*
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Time Factors

Substances

  • Antineoplastic Agents
  • Enoxaparin
  • Hyaluronan Receptors
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc