Antiangiogenic activity of orally absorbable heparin derivative in different types of cancer cells

Pharm Res. 2009 Dec;26(12):2667-76. doi: 10.1007/s11095-009-9989-9. Epub 2009 Oct 15.

Abstract

Purpose: Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models.

Methods: We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murine squamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD.

Results: Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue.

Conclusion: Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxycholic Acid / analogs & derivatives*
  • Deoxycholic Acid / pharmacology
  • Deoxycholic Acid / therapeutic use
  • Disease Models, Animal
  • Heparin, Low-Molecular-Weight / analogs & derivatives*
  • Heparin, Low-Molecular-Weight / pharmacology
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure

Substances

  • Angiogenesis Inhibitors
  • Heparin, Low-Molecular-Weight
  • LMWH-DOCA conjugate
  • Deoxycholic Acid