Interleukin 10 abolishes the growth inhibitory effects of all-trans retinoic acid on human myeloma cells.
Recently, it was disclosed that all-trans retinoic acid (ATRA) inhibits myeloma cell growth by downregulating the interleukin 6 (IL-6)/IL-6 receptor (IL-6R) auto/paracrine loop, and upregulating p21/Cip1 cyclin-dependent kinase inhibitor (CDK-I), thereby inducing apoptosis with a decrease in Bcl-2 protein expression. To elucidate and generalize the effects of ATRA on the proliferation and cellular biology of myeloma cells, 12 human myeloma cell lines established in our laboratory were utilized. Two out of the 12 lines showed enhanced growth on supplementation of ATRA and were characterized by IL-10 production, downregulation of membrane Fas and reduced upregulation of p21/Cip1 CDK-I message. These characteristics may prove important for the clinical use of ATRA and should be considered before starting ATRA therapy for myeloma.
Otsuki
Takemi
T
Department of Hygiene, Division of Hematology, Kawasaki Medical School, Kurashiki, Japan. takemi@med.kawasaki-m.ac.jp
Yata
Kenichiro
K
Sakaguchi
Haruko
H
Kurebayashi
Junichi
J
Matsuo
Yoshinobu
Y
Uno
Masako
M
Fujii
Tomohiro
T
Eda
Sakura
S
Isozaki
Yumika
Y
Yawata
Yoshihito
Y
Yamada
Osamu
O
Wada
Hideho
H
Sugihara
Takashi
T
Ueki
Ayako
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019014:fas Receptor; D016753:Interleukin-10; D014212:Tretinoin; D016203:CDC2 Protein Kinase