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Antiangiogenic and apoptotic properties of a novel amphiphilic folate-heparin-lithocholate derivative having cellular internality for cancer therapy.
- Source :
-
Pharmaceutical research [Pharm Res] 2007 Apr; Vol. 24 (4), pp. 705-14. Date of Electronic Publication: 2007 Feb 21. - Publication Year :
- 2007
-
Abstract
- Purpose: Anitangiogenic and apoptotic properties of a novel chemically modified heparin derivative with low anticoagulant activity were evaluated on the experimental in vitro and in vivo model.<br />Materials and Methods: Heparin-lithocholate conjugate (HL) was initially synthesized by covalently bonding lithocholate to heparin. Folate-HL conjugate (FHL) was further synthesized by conjugating folate to HL. Antiangiogenic and apoptotic abilities of HL and FHL were characterized in vitro and in vivo experimentations.<br />Results: Compared to unmodified heparin, both HL and FHL represented a low anticoagulant activity (38 and 28%, respectively). HL and FHL maintained antiangiogenic activity even further modification from the results of Matrigel plugs assay. FHL specifically induced apoptosis on KB cells having highly expressed folate receptor after cellular internalization. Both administered HL and FHL had similar antiangiogenic activity and inhibitory effect on tumor growth in vivo although FHL induced higher apoptosis on tumor tissues.<br />Conclusions: In vivo tumor growth inhibition was possibly due to the decrease of vessel density and apoptotic cell death, although antiangiogenic effect of FHL seemed more actively affected on growth inhibition than apoptotic potential in vivo system. Thus, Low anticoagulant FHL having antiangiogenic and apoptotic properties would provide benefits for the development of a new class of anticancer agent.
- Subjects :
- Angiogenesis Inhibitors chemical synthesis
Angiogenesis Inhibitors metabolism
Angiogenesis Inhibitors therapeutic use
Animals
Anticoagulants pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents metabolism
Antineoplastic Agents therapeutic use
Carrier Proteins metabolism
Cell Line, Tumor
Cell Survival drug effects
Collagen
Disease Models, Animal
Drug Combinations
Endocytosis
Female
Folate Receptors, GPI-Anchored
Heparin chemical synthesis
Heparin metabolism
Heparin pharmacology
Heparin therapeutic use
Humans
Laminin
Lithocholic Acid chemical synthesis
Lithocholic Acid metabolism
Lithocholic Acid pharmacology
Lithocholic Acid therapeutic use
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Neoplasms, Experimental blood supply
Neoplasms, Experimental pathology
Neoplasms, Experimental physiopathology
Neovascularization, Pathologic chemically induced
Proteoglycans
Receptors, Cell Surface metabolism
Time Factors
Xenograft Model Antitumor Assays
Angiogenesis Inhibitors pharmacology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Heparin analogs & derivatives
Lithocholic Acid analogs & derivatives
Neoplasms, Experimental drug therapy
Neovascularization, Pathologic prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0724-8741
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 17318418
- Full Text :
- https://doi.org/10.1007/s11095-006-9190-3