Amyrin esters induce cell death by apoptosis in HL-60 leukemia cells.

Autor: Barros FW; Departament of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará 60430-270, Brazil., Bandeira PN, Lima DJ, Meira AS, de Farias SS, Albuquerque MR, dos Santos HS, Lemos TL, de Morais MO, Costa-Lotufo LV, Pessoa Cdo Ó
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2011 Feb 01; Vol. 19 (3), pp. 1268-76. Date of Electronic Publication: 2010 Dec 09.
DOI: 10.1016/j.bmc.2010.12.016
Abstrakt: Four derivatives of an α,β-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,β-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3μM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.
(Copyright © 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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