| Enhanced anticancer activity of glutamate prodrugs of all-trans retinoic acid. | |
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MedLine Citation:
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PMID: 19814868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: All-trans retinoic acid (ATRA), an active metabolite of vitamin A, is widely used in the treatment of acute promyelocytic leukaemia and myelodysplastic syndrome. However, its high lipophilicity is thought to be responsible for the slow dissolution and low bioavailability following oral administration. In order to obtain compounds with better solubility characteristics to improve the transportation and bioavailability of ATRA, derivatives of ATRA containing glutamic acid or its sodium salt were synthesised. METHODS: The ATRA derivatives synthesised - all-trans retinoyl glutamate (RAE) and all-trans retinoyl sodium glutamate (RAENa(2)) - were characterised in terms of melting point, optical rotation, mass spectrometry, NMR and partition coefficient. A liposomal preparation formed from RAE was characterised by particle size and zeta potential. The anti-tumour activity of RAE and RAENa(2) was compared with that of ATRA in mice bearing S(180) tumours and their effects on the cell cycle were determined in human pro-myelocytic leukaemia HL-60 cells. KEY FINDINGS: RAE and RAENa(2) were more active than ATRA against tumour growth. Flow cytometry indicated that RAE and RAENa(2) induced HL-60 cell cycle arrest, similar to ATRA. DNA fragmentation studies suggested that apoptosis may be one of the mechanisms responsible for the anti-tumour activities. CONCLUSIONS: The two derivatives of ATRA, RAE and RAENa(2), exhibited improved aqueous solubility and were more effective in mice bearing S(180) tumours. |
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Authors:
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Chunying Cui; Yunwei Zhang; Lili Wang; Hu Liu; Guohui Cui |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 61 ISSN: 2042-7158 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-09 Completed Date: 2010-01-21 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1353-8 Citation Subset: IM |
Affiliation:
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School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology* Cell Cycle / drug effects Cell Line, Tumor DNA Fragmentation / drug effects Glutamates / chemical synthesis, chemistry, pharmacology* HL-60 Cells Humans Liposomes / administration & dosage Mice Prodrugs / administration & dosage, chemical synthesis, chemistry, pharmacology* Tretinoin / analogs & derivatives*, chemical synthesis, chemistry, pharmacology* Tumor Burden / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Glutamates; 0/Liposomes; 0/Prodrugs; 0/retinoyl glutamate; 302-79-4/Tretinoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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