Heparin induces apoptosis through suppression of AKt in oral squamous cell carcinoma cells

Anticancer Res. 2009 Apr;29(4):1079-88.

Abstract

Background: Heparin is a polysulfated glycosaminoglycan that has been shown to have antiproliferative and apoptotic effects in addition to its anticoagulant effects.

Materials and methods: The present work investigated the effects of unfractioned heparin (UFH) on cell growth and apoptosis in four oral squamous cell carcinoma (SCC) cell lines and the mechanism(s) underlying its actions using MTT assay, Annexin-V-FITC and Western blotting.

Results: Treatment with UFH resulted in significant reduction in cell viability and increase in apoptosis in three of the four tested cell lines. Further, such treatment resulted in a significant decrease in phosphorylated AKt, and consequently led to activation of the mitochondrial pathway in heparin-sensitive cells. Moreover, pretreatment with UFH significantly increased the apoptosis induced by cisplatin.

Conclusion: These findings indicate that heparin induces apoptosis through suppression of AKt, and suggest a potential utility of heparin for development of less toxic chemotherapy in treatment of oral SCC.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Fibrinolytic Agents / pharmacology*
  • Heparin / pharmacology*
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • bcl-Associated Death Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAD protein, human
  • Fibrinolytic Agents
  • bcl-Associated Death Protein
  • Heparin
  • Proto-Oncogene Proteins c-akt
  • Cisplatin