Chemopreventive activities of C-glucuronide/glycoside analogs of retinoid-o-glucuronides against breast cancer development and growth

R. W. Curley, H. Abou-Issa, M. J. Panigot, J. J. Repa, M. Clagett-Dame, G. Alshafie

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The O-glucuronide analog of N-(4-hydroxyphenyl)retinamide (4-HPROG) has shown a greater chemopreventive activity than the parent N-(4-hydroxyphenyl)retinamide (4-HPR). However, this compound is relatively unstable. In order to improve stability and efficacy, we have prepared a number of stable C-linked analogs of 4-HPROG (C-phenyl and C-benzyl glucuronosyl, glucosyl, and xylosyl analogs). These analogs are stable toward acid hydrolysis and the glucuronosyl analogs resist the actions of β-glucuronidase. The analogs were prescreened for their antiproliferative potential in vitro using cultured human MCF-7 breast cancer cells. Selected analogs were then evaluated for their ability to inhibit the development and growth of tumors in the 7,12-dimethylbenzanthracene-induced rat mammary tumor model. Although the stable C-linked analogs bound poorly to the nuclear retinoic acid receptors, many showed more potency than the less stable 4-HPROG in inhibiting tumor incidence and multiplicity in vivo. The glucuronide/glucoside analogs are more potent than the xylosides, and the C-benzyl more effective than the C-phenyl analogs. The higher potency of at least two C-linked analogs (retinamidobenzyl glucuronide and retinami- dobenzyl glucose) suggests that these analogs may have a chemopreventive advantage over the parent retinamide and its natural O-glucuronide.

Original languageEnglish (US)
Pages (from-to)757-764
Number of pages8
JournalAnticancer Research
Volume16
Issue number2
StatePublished - Dec 1 1996

Keywords

  • Breast cancer
  • Cancer chemoprevention
  • Retinoid glucuronides
  • Retinoids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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