Glucocorticoid hormone renders a rat glioma cell line sensitive to a G1 phase block by microtubule disrupting agents.
1. Hydrocortisone, a glucocorticoid hormone, renders C6 rat glioma cells (clone ST1) sensitive to a block by colchicine or nocodazole (microtubule disrupters) at the G1 phase of the cell cycle. Restimulation of DNA synthesis in hydrocortisone-treated glioma cells arrested at G0/G1 phase by serum step-down is inhibited (85%) by colchicine (0.4 microgram/ml) added during the first 6 h of restimulation by serum step-up. 2. Exponentially growing, hydrocortisone-treated glioma cell cultures when subjected to colchicine treatment accumulated mitoses for 16.5 h, resulting in two types of cell cycle blocked cells: mitotic (round, detached or poorly attached) and G1 phase cells (flat and well attached to the solid substrate). The latter reinitiated DNA synthesis 15 h after colchicine withdrawal. Plating efficiency assays showed that while the colchicine block was highly toxic for mitotic cells, the survival of G1 phase arrested cells was not affected. In conclusion, in these rat glioma cells, hydrocortisone reversibly makes G1 phase progress dependent on microtubule integrity. 3. Restimulation of DNA synthesis in "normal" 3T3 fibroblasts arrested at the G0/G1 phase by serum deprivation was not inhibited by colchicine when the drug was added at the time of serum step-up. However, 70% inhibition occurred when colchicine was added at 10 h of serum stimulation.
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects; D005910:Glioma / Q000473:pathology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D007399:Interphase; D051379:Mice; D008870:Microtubules / Q000502:physiology; D008938:Mitosis; D009374:Neoplasms, Experimental / Q000473:pathology; D015739:Nocodazole; D051381:Rats
D001562:Benzimidazoles; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D015739:Nocodazole; D003078:Colchicine; D006854:Hydrocortisone