HSP90 inhibitor 17AAG causes apoptosis in ATRA-resistant acute promyelocytic leukemia cells.
The effects of a novel heat shock protein inhibitor, 17AAG, on established APL cell lines (NB4 and R1) were analyzed. 17AAG induces apoptosis in APL cell lines both sensitive (NB4) and resistant (R1) to ATRA after 72 h of incubation. Apoptosis occurs by a mechanism different than ATRA-mediated response, as the cells do not undergo differentiation before apoptosis. Analysis of bax and bcl-2 shows that pro-apoptotic (bax) and anti-apoptotic (bcl-2) proteins are decreased in expression after incubation with 17AAG. We believe this data supports potential clinical use of agents that target HSP90 in APL patients failing conventional therapy.
Meyer
Paul N
PN
Loyola University Medical Center, Department of Pathology, 2160 S First Avenue, Maywood, IL 60153, USA.
Roychowdhury
Shantanu
S
Kini
Ameet R
AR
Alkan
Serhan
S
D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin; D014212:Tretinoin