Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands.
3,5,3'-Triiodo-L-thyronine (T3) potentiates apoptosis during the all-trans-retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T3 potentiates G1 arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G1 arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T3. However, T3 or HX600 or both do not affect the expression of CD11b. T3 does not alter the amount of mRNAs of various members of the bcl-2 family. T3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T3 with an RXR-specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia.
Hara
M
M
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Suzuki
S
S
Mori
J
J
Yamashita
K
K
Kumagai
M
M
Sakuma
T
T
Kakizawa
T
T
Takeda
T
T
Miyamoto
T
T
Ichikawa
K
K
Hashizume
K
K
D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology; D018845:CD11 Antigens / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D003984:Dibenzazepines / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells / Q000473:pathology*; D006801:Humans; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists*; D014212:Tretinoin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D001565:Benzoates; D018845:CD11 Antigens; D003984:Dibenzazepines; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D014284:Triiodothyronine; C061133:tamibarotene; C104181:HX 600; D014212:Tretinoin