Inhibition of DNA synthesis in human gliomas by roscovitine.
The early effect of 1-100 microM roscovitine, a purine analogue and cyclin-dependent kinase inhibitor, was studied on tissue specimens from eight human malignant gliomas. The tissue was incubated immediately after resection with DMEM containing [3H]methylthymidine plus vehicle alone or the proper concentration of roscovitine for 30-90 min. The DNA synthesis rate was assessed by measurement of [3H]methylthymidine incorporation into trichloroacetic acid insoluble material/mg protein/min. In all gliomas, 100 microM roscovitine inhibited DNA synthesis by 71-97% (average 89 +/- 8%, p<0.0001). This inhibitory effect of roscovitine appeared within 30 min of incubation and was concentration dependent.
Yakisich
J S
JS
Applied Biochemistry, Clinical Research Center, Huddinge, Sweden.
Boethius
J
J
Lindblom
I O
IO
Wallstedt
L
L
Vargas
V I
VI
Sidén
A
A
Cruz
M H
MH
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011687:Purines / Q000627:therapeutic use*; D000077546:Roscovitine
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011687:Purines; D000077546:Roscovitine