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.
Various natural and synthetic retinoids have been studied for their activity in two biological systems: (a) their activity as inhibitors of methylcholanthrene-induced neoplastic transformation in the C3H/10T1/2 clone 8 mouse fibroblast line (System 1); and (b) their ability to increase the degree of adhesion of C3H/10T1/2 clone 8 cells to a plastic substrate (System 2). These activities were then 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 shown to be inactive in System 1 had little or no activity in System 2. However, the ability of retinoids to cause increased adhesion could not be correlated with Systems 1 or 3 in all cases. For instance, retinyl acetate was highly active in Systems 1, 2, and 3, whereas retinylidene dimedone was highly active in Systems 1 and 3 but weakly active in System 2. Conversely, N-(4-hydroxyphenyl)retinylamide was highly active in Systems 1 and 3 but caused a decrease in System 2. The lack of activity of 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.
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004224:Diterpenes; D017313:Fenretinide; D015474:Isotretinoin; D008748:Methylcholanthrene / Q000037:antagonists & inhibitors*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D012176:Retinoids; D000084562:Retinyl Esters; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology
D000577:Amides; D004224:Diterpenes; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; D017313:Fenretinide; C009675:vitamin A acid ethylamide; C009166:retinol acetate; D008748:Methylcholanthrene; D014212:Tretinoin; C023048:retinylidene dimedone; C027159:N-benzoylretinylamine; D015474:Isotretinoin