Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells.
Progesterone plays a pivotal role in controlling uterine leiomyoma growth. The authors review studies they conducted to evaluate the comparative effects of asoprisnil on proliferation, apoptosis, and growth factor expression in cultured leiomyoma and normal myometrial cells. Treatment with asoprisnil decreased the proliferating cell nuclear antigen-positive rate and the number of viable cells and increased the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling- positive rate in cultured leiomyoma cells in a dose-dependent manner ( P < .05). Similarly, asoprisnil decreased Bcl-2 expression and increased cleaved caspase-3 and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase in leiomyoma cells but not in normal myometrial cells. Similarly, asoprisnil decreased epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and transforming growth factor (TGF) beta mRNA and protein expression, as well as EGF receptor, IGF-IR alpha, and TGF RII protein expression in leiomyoma cells but not in cultured normal myometrial cells. These results suggest that asoprisnil selectively inhibits proliferation by downregulating the growth factors and their receptor expression and induces apoptosis in leiomyoma cells without affecting proliferation and apoptosis in normal myometrial cells.
Ohara
Noriyuki
N
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Morikawa
Akira
A
Chen
Wei
W
Wang
Jiayin
J
DeManno
Deborah A
DA
Chwalisz
Kristof
K
Maruo
Takeshi
T
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010091:Oximes / Q000494:pharmacology*; D010766:Phosphorylation; D011374:Progesterone / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
D004963:Estrenes; D036341:Intercellular Signaling Peptides and Proteins; D010091:Oximes; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D018125:Receptors, Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; C488516:asoprisnil; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II