Pomolic acid may overcome multidrug resistance mediated by overexpression of anti-apoptotic Bcl-2 proteins.
Multidrug resistance (MDR) is multifactorial and may be mediated by overexpression of anti-apoptotic proteins. This paper investigated whether pomolic acid (PA) was able to overcome resistance mediated by overexpression of Bcl-2 or BcL-xL. The results obtained showed that overexpression of these proteins partially inhibited the PA-induced apoptosis, loss of mitochondrial membrane potential and caspase -3 and -9 activation observed in HL-60/neo. Since Bcl-2 transfected cell lines were shown to be quite resistant to a series of chemotherapeutic agents, the data presented call attention to the possible clinical significance of PA as an anti-MDR drug.
Fernandes
Janaina
J
Instituto de Biofísica Carlos Chagas Filho, Laboratório de Imunoparasitologia, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Cidade Universitária, 21949-900 Rio de Janeiro, RJ, Brazil.
Weinlich
Ricardo
R
Castilho
Rachel Oliveira
RO
Amarante-Mendes
Gustavo Pessini
GP
Gattass
Cerli Rocha
CR
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C115535:pomolic acid; D009828:Oleanolic Acid; D053148:Caspase 3; D053453:Caspase 9