The novel retinoid AHPN/CD437 induces a rapid but incomplete apoptotic response in human myeloma cells.
The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) appears to possess an apoptotic activity superior to classical retinoids in vitro as in vivo. Numerous studies have shown that CD437-induced apoptosis is independent of its nuclear receptor activity, suggesting that CD437 might have a unique mechanism of action. The purpose of this study was to compare CD437- and all-trans retinoic acid (atRA)-induced cell death. CD437 provoked a rapid apoptotic phenotype immediately followed by secondary necrosis in RPMI 8226, U266 and L363 human myeloma cell lines. Nuclear apoptotic features were observed upon both CD437 and atRA treatments. In contrast, membrane blebbing and the subsequent formation of apoptotic bodies, a classical apoptotic event, was only observed upon atRA treatment. In addition, CD437, contrary to atRA, was unable to induce tissue transglutaminase (tTG), an intracellular enzyme involved in the formation of cross-linked protein polymers contributing to apoptotic morphological changes. Taken together, these data suggest that CD437 induces rapid but incomplete apoptotic phenotype in human myeloma cells.
Joseph
Bertrand
B
INSERM U459, Faculté de Médecine, 1 Place Verdun, F-59045 Cedex, Lille, France.
Marchetti
Philippe
P
Lefebvre
Olga
O
Schraen-Maschke
Suzanna
S
Méreau-Richard
Claude
C
Formstecher
Pierre
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D034921:Lamin Type B / Q000032:analysis; D009101:Multiple Myeloma; D012333:RNA, Messenger; D012176:Retinoids / Q000494:pharmacology*; D011503:Transglutaminases / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology; D014463:Ultrasonography
D000970:Antineoplastic Agents; C099555:CD 437; D034921:Lamin Type B; D012333:RNA, Messenger; D012176:Retinoids; D014212:Tretinoin; D011503:Transglutaminases; C105804:transglutaminase 1