Retinyl substituted-benzyl ethers. Inhibition of mammary carcinogenesis by retinyl 3,4,5-trimethoxybenzyl ether (RTMBE)

• Published in: Anti-cancer drug design Vol. 13; no. 3; p. 159
• Main Authors: Shealy, Y F, Frye, J L, Hill, D L, Sani, B P, Rogers, T S, Riordan, J M, Krauth, C A, Lin, T H, Eto, I, Grubbs, C J
• Format: Journal Article
• Language: English
• Published: United States 01-04-1998
• Subjects: Administration, Oral; Animals; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - pharmacokinetics; Anticarcinogenic Agents - pharmacology; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Liver - metabolism; Magnetic Resonance Spectroscopy; Mammary Glands, Animal - metabolism; Mammary Neoplasms, Experimental - prevention & control; Mass Spectrometry; Mice; Molecular Structure; Rats; Rats, Sprague-Dawley; Spectrophotometry, Ultraviolet; Tissue Distribution; Vitamin A - analogs & derivatives; Vitamin A - chemistry; Vitamin A - pharmacokinetics; Vitamin A - pharmacology
• ISSN: 0266-9536

Recently, we reported that retinyl 2-propynyl ether (RPE) inhibits MNU-induced mammary cancer in rats and is less toxic than RME and retinyl acetate. The preparation and biological investigations of retinyl ethers have now been extended to retinyl substituted-benzyl ethers, some of which bind to cellular retinol-binding protein. In long-term (160-180 days) experiments, retinyl 3,4,5-trimethoxybenzyl ether (RTMBE) has been shown to be active against MNU-induced mammary cancer in Sprague-Dawley rats. In effectiveness, RTMBE is comparable, at least, to retinyl acetate; but, unlike retinyl acetate, RTMBE is comparatively non-toxic to rats and mice, is not converted enzymatically to retinol, and does not cause significant increases in retinyl palmitate concentrations in the liver. RTMBE reaches high concentrations in mammary tissue. Two of the four RTMBE congeners that were evaluated in 90 day studies were moderately effective in inhibiting mammary carcinogenesis.