Effect of the Novel Prostaglandin A1 Derivative TEI-6363 on ROS17/2.8 Cell Differentiation In Vitro

The Japanese Journal of Pharmacology

Yoshiaki Azuma¹  Hiroshi Uno¹  Tomohiro Ohta¹  Yoshihiro Izawa¹  Daishiro Miura¹  Mamoru Kiyoki¹ 

[1] Teijin Institute for Bio-Medical Research,4-3-2 Asahigaoka,Hino,Tokyo 191-8512,Japan

关键词: Prostaglandin;    Cyclopentenone;    Osteoblast;    G1 arrest;    Differentiation;   

DOI  :  10.1254/jjp.83.246

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)The effect of TEI−6363(5−[E−4−N, N−dimethylaminophenylmethylene]−4−hydroxy−2−[1−methyl imidazole−2−ilthio]−4−[4−phenylbutyl]−2−cyclopentenone), a chemically synthesized prostaglandin A1 derivative, on cell proliferation and osteoblastic differentiation was investigated concurrently.ROS17/2.8 cells(a rat osteosarcoma−derived cell line)were treated with TEI−6363 at two concentrations, 10-7 and 10-6M, and viable cells were counted to assess cytotoxic effects and determine the growth curve.After 96 h of treatment, there was no evidence of any effect of TEI−6363 on cell viability at either concentration.However, a clear inhibitory effect on cell proliferation was observed after treatment with 10-6M TEI−6363 for 24 h or longer.A pulsetreatment experiment showed that TEI−6363 induced the inhibition of proliferating ROS17/2.8 cells 24 h after addition.The inhibition of proliferation was associated with G1−arrest demonstrated by flow cytometric analysis, and incorporation of [3H]thymidine by ROS17/2.8 cells was decreased.Osteoblastic differentiation(assessed on the basis of increased alkaline phosphatase activity and collagen synthesis)was induced by TEI−6363 treatment at 10-6M following G1−arrest and inhibition of cell proliferation.These results suggest that TEI−6363 arrested the cell cycle of ROS17/2.8 cells at the G1 phase and induced osteoblastic differentiation.These results did not appear to be dependent on a marked cytotoxic effect.

【 授权许可】

Unknown