Antimetastatic effect of an orally active heparin derivative on experimentally induced metastasis

Dong Yun Lee, Kyeongsoon Park, Sang Kyoon Kim, Rang Woon Park, Ick Chan Kwon, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Purpose: Orally active anticancer drugs have great advantages for the treatment of cancer. Compelling data suggest that heparin exhibits critical antimetastatic effects via interference with P-selectin-mediated cell-cell binding. However, heparin should be given parenterally because it is not orally absorbed. Here, we evaluated the inhibitory effect of orally absorbable heparin derivative (LHD) on experimentally induced metastasis. Experimental Design: We developed LHD, which is a chemical conjugate of low molecular weight heparin and deoxycholic acid, and measured the plasma concentration of LHD after oral administration. To evaluate the antimetastatic effect of LHD, we carried out experimental lung metastasis assays in vivo using murine melanoma or human lung carcinoma cells and interruption assay between murine melanoma cells and activated platelets and human umbilical vascular endothelial cells in vitro. Results: In mice, the plasma concentration was ~ 7 u,g/mL at 20 minutes after oral administration of LHD (10 mg/kg), indicating that bleeding was not induced at this dose. Interestingly, we found that LHD dramatically attenuated metastasis experimentally induced by murine melanoma or human lung carcinoma cells and that its antimetastatic activity was attributed to the interruption of the interactions between melanoma cells and activated platelets and between melanoma cells and human umbilical vascular endothelial cells by blocking selectin-mediated interactions. Furthermore, it prevented tumor growth in secondary organs. Conclusions: On the basis of these findings, the present study shows the possibility of LHD as a suitable first-line anticancer drug that can be used for preventing metastasis and recurrence because it has therapeutic potential as an antimetastatic drug, has lower side effects, and can be orally absorbed.

Original languageEnglish
Pages (from-to)2841-2849
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number9
DOIs
Publication statusPublished - 2008 May 1
Externally publishedYes

Fingerprint

Heparin
Neoplasm Metastasis
Melanoma
Umbilicus
Lung
Oral Administration
Blood Platelets
Endothelial Cells
Pharmaceutical Preparations
Carcinoma
Selectins
P-Selectin
Neoplasms
Research Design
Hemorrhage
Recurrence
Therapeutics
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lee, D. Y., Park, K., Kim, S. K., Park, R. W., Kwon, I. C., Kim, S. Y., & Byun, Y. (2008). Antimetastatic effect of an orally active heparin derivative on experimentally induced metastasis. Clinical Cancer Research, 14(9), 2841-2849. https://doi.org/10.1158/1078-0432.CCR-07-0641

Antimetastatic effect of an orally active heparin derivative on experimentally induced metastasis. / Lee, Dong Yun; Park, Kyeongsoon; Kim, Sang Kyoon; Park, Rang Woon; Kwon, Ick Chan; Kim, Sang Yoon; Byun, Youngro.

In: Clinical Cancer Research, Vol. 14, No. 9, 01.05.2008, p. 2841-2849.

Research output: Contribution to journalArticle

Lee, Dong Yun ; Park, Kyeongsoon ; Kim, Sang Kyoon ; Park, Rang Woon ; Kwon, Ick Chan ; Kim, Sang Yoon ; Byun, Youngro. / Antimetastatic effect of an orally active heparin derivative on experimentally induced metastasis. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 9. pp. 2841-2849.
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