STRUCTURE-ACTIVITY-RELATIONSHIPS AMONG VARIOUS RETINOIDS AND THEIR ABILITY TO INHIBIT NEOPLASTIC TRANSFORMATION AND TO INCREASE CELL-ADHESION IN THE C3H-10T1/2 CL8 CELL-LINE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (9) , 3141-3146
Abstract
Various natural and synthetic retinoids were studied for their activity in the following biological systems: their activity as inhibitors of methylcholanthrene-induced neoplastic transformation in the C3H/10T1/2 clone 8 mouse fibroblast line (System 1), and their ability to increase the degree of adhesion of C3H/10T1/2 clone 8 cells to a plastic substrate (System 2). These activities were compared with their known activity in maintaining epithelial differentiation (System 3). With the notable exception of retinoic acid and 13-cis-retinoic acid, which were inactive in Systems 1 and 2, an excellent correlation was observed between activities in Systems 1 and 3 for retinyl acetate, N-(4-hydroxyphenyl)retinamide, retinylidene dimedone, N-ethylretinamide and N-benzoylretinylamine. Compounds inactive in System 1 had little or no activity in System 2. The ability of retinoids to cause increased adhesion could not be correlated with Systems 1, or 3 in all cases. Retinyl acetate was highly active in Systems 1, 2 and 3; retinylidene dimedone was highly active in Systems 1 and 3 but weakly active in System 2. N-(4-hydroxyphenyl)retinylamide was highly active in Systems 1 and 3 but caused a decrease in System 2. The lack of activity of retinoic acid isomers in the C3H/10T1/2 clone 8 system is paradoxical and may provide important information on requirements for their activation and/or transport.