Comparative Effects of SPRM Asoprisnil (J867) on Proliferation, Apoptosis, and the Expression of Growth Factors in Cultured Uterine Leiomyoma Cells and Normal Myometrial Cells

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2007-12, Vol.14 (8_suppl), p.20-27
• Main Authors: Ohara, Noriyuki, Morikawa, Akira, Wei Chen, Jiayin Wang, DeManno, Deborah A., Chwalisz, Kristof, Maruo, Takeshi
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Down-Regulation; Epidermal Growth Factor - metabolism; Estrenes - pharmacology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Insulin-Like Growth Factor I - metabolism; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Leiomyoma - metabolism; Leiomyoma - pathology; Medical sciences; Myometrium - drug effects; Myometrium - metabolism; Myometrium - pathology; Oximes - pharmacology; Phosphorylation; Progesterone - metabolism; Proliferating Cell Nuclear Antigen - metabolism; Protein-Serine-Threonine Kinases - drug effects; Protein-Serine-Threonine Kinases - metabolism; Receptor, Epidermal Growth Factor - drug effects; Receptor, Epidermal Growth Factor - metabolism; Receptor, IGF Type 1 - drug effects; Receptor, IGF Type 1 - metabolism; Receptors, Progesterone - drug effects; Receptors, Progesterone - metabolism; Receptors, Transforming Growth Factor beta - drug effects; Receptors, Transforming Growth Factor beta - metabolism; RNA, Messenger - metabolism; Time Factors; Transforming Growth Factor beta3 - metabolism; Tumor Cells, Cultured; Tumors; Uterine Neoplasms - metabolism; Uterine Neoplasms - pathology
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719107311464

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) β mRNA and protein expression, as well as EGF receptor, IGF-IRα, 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.