Abolition of L1210 clonogeneticy and G1 arrest by retinoic acid and 1,25-dihydroxyvitamin D3

• Published in: Cancer letters Vol. 27; no. 2; p. 125
• Main Authors: Moqattash, S, Lutton, J D, Chiao, J W, Levere, R D
• Format: Journal Article
• Language: English
• Published: Ireland 01-06-1985
• Subjects: Animals; Calcitriol - pharmacology; Cell Cycle - drug effects; Cell Survival - drug effects; Cells, Cultured; Leukemia L1210 - pathology; Mice; Mice, Inbred DBA; Tretinoin - pharmacology
• ISSN: 0304-3835
• DOI: 10.1016/0304-3835(85)90101-6

Results from this study demonstrate that L1210 lymphocytic leukemia cells generate tumor cell colonies in plasma clot culture, and that the cells can be maintained in suspension cultures for 3 days without a loss in viability or clonogeneticy. Additions of 10(-5)-10(-8) M retinoic acid (RA) or 1,25-dihydroxyvitamin D3 (1,25VD3) to suspension cultures had no effect on cell viability. However, there was an increase in cellular adherence, nuclear chromatin condensation and a depression of clonogenic potential by 99-25%. Flow cytometry analysis of 3-day suspension cultures revealed that both RA or 1,25VD3 promoted an accumulation of cells in G1-phase, with 1,25VD3 being the most effective. For example, treatment with 10(-5) M 1,25VD3 yielded a 76.7% G1-phase accumulation as contrasted with 36.3% for controls, and associated with this G1-shift was a 97% loss in clonogeneticy. Treatment with RA gave a slightly less G1-phase accumulation (64%), which was associated with a 74% loss in clonogeneticy. It is suggested that RA and 1,25VD3 exert their cell cycle and anti-tumor effects by modulating cellular events or metabolism, or by promoting the accumulation of a quiescent cell population.