Effect of the novel prostaglandin A1 derivative TEI-6363 on ROS17/2.8 cell differentiation in vitro.
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(-6) M, 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(-6) M TEI-6363 for 24 h or longer. A pulse-treatment 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(-6) M 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.
Miura
D
D
Teijin Institute for Bio-Medical Research, Hino, Tokyo, Japan.
Uno
H
H
Azuma
Y
Y
Ohta
T
T
Kiyoki
M
M
Izawa
Y
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D011454:Prostaglandins A / Q000737:chemistry* / Q000494:pharmacology*; D011455:Prostaglandins A, Synthetic; D051381:Rats; D014407:Tumor Cells, Cultured
C417086:5-(4-N,N-dimethylaminophenylmethylene)-4-hydroxy-2-(1-methylimidazol-2-ylthio)-4-(4-phenylbutyl)-2-cyclopentenone; D011454:Prostaglandins A; D011455:Prostaglandins A, Synthetic; D003094:Collagen; D000469:Alkaline Phosphatase; C100573:prostaglandin A1