Effects of novel retinoids on growth and differentiation of a rhabdomyosarcoma cell line.

The influence of all-trans-retinoic acid-beta-D-glucopyranosylester, all-trans-retinoic acid-beta-D-galactopyranosylester, methyl-(1-O-retinoyl-beta-D-glucopyranoside)uronate and all trans-retinyl-beta-D-glucuronide were investigated on the celle line BA-HAN-1C. This clonal cell line was derived from a dimethylbenzanthracene induced rhabdomyosarcoma in the rat. The tumor cells were incubated for 5 days with medium which was supplemented with various concentrations of the different compounds. The action of the retinoids were measured by comparing the cellular growth and the creatine kinase activity (as differentiation marker) with an supplemented cell line. The retinoids which are based on all-trans-retinoic acid (all-trans-retinoic acid-beta-D-glucopyranosylester, all-trans-retinoic acid-beta-D-galactopyranosylester, methyl-(1-O-retinoyl-beta-D-glucopyranoide)uronate and their chemical precursors) showed similar biological effects as all-trans-retinoic acid and could be used in higher concentrations than retinoic acid without the appearance of toxic effects. The all-trans-retinyl-beta-D-glucuronide derivatives did not show any influence on the cell growth and their creatinine kinase activity. With respect to the effects of the compounds two hypothesis about their function were possible: They act as a whole molecule, or: they are bound to a receptor where the really effective substance, all-trans-retinoic acid is released from the molecule by hydrolytic cleavage as required. Investigations with the carbohydrates D-glucose, D-galactose and D-uronic acid disproved the second theorie because these substances enormously support the growth of the tumor cells. The effectively of the free all-trans-retinoic acid would have been diminished by these components. However, this effect did not appear if hydrolysis is considered.