Lee, Dong Yun Park, Kyeongsoon Kim, Sang Kyoon Park, Rang-Woon Kwon, Ick Chan Kim, Sang Yoon Byun, Youngro 2024-01-20T23:30:30Z 2024-01-20T23:30:30Z 2021-09-03 2008-05-01 1078-0432 https://pubs.kist.re.kr/handle/201004/133502 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 similar to 7 mu 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. English AMER ASSOC CANCER RESEARCH MOLECULAR-WEIGHT HEPARIN P-SELECTIN DEOXYCHOLIC-ACID CELL-ADHESION CHEMICAL CONJUGATE TUMOR-GROWTH CANCER ABSORPTION DELIVERY CARCINOMA Antimetastatic effect of an orally active heparin derivative on experimentally induced metastasis Article 10.1158/1078-0432.CCR-07-0641 1 CLINICAL CANCER RESEARCH, v.14, no.9, pp.2841 - 2849 CLINICAL CANCER RESEARCH 14 9 2841 2849 scie scopus 000255616300041 2-s2.0-52049121633 Oncology Oncology Article MOLECULAR-WEIGHT HEPARIN P-SELECTIN DEOXYCHOLIC-ACID CELL-ADHESION CHEMICAL CONJUGATE TUMOR-GROWTH CANCER ABSORPTION DELIVERY CARCINOMA