Chemotherapeutic evaluation of N-(4-hydroxyphenyl) retinamide-O-glucuronide in the rat mammary tumor model.

Abstract

The growth inhibitory effects of N-(4- Hydroxyphenyl) retinamide (4-HPR) and its glucuronide derivative, N-(4-Hydroxyphenyl) retinamide-O-glucuronide (4-HPROG) on established DMBA induced rat mammary tumors were compared. The results indicate that the glucuronide analog had a greater antitumor potency than equimolar concentration of the free retinoid. Tumor regression occurred in 75% of the rats fed 2 mmol/Kg diet of 4-HPROG. In a 6-week study, the maximum tolerated dietary dose (MTD) was found to be 3.5 mmol/Kg diet for 4-HPR and 5 mmol/Kg diet in the case of 4-HPROG. The higher potency and lower toxicity of the glucuronide suggests that this conjugate may have an in vivo chemotherapeutic advantage over the parent free retinoid.

• Authors: H Abou-Issa, R W Curley Jr, M J Panigot, S N Tanagho, B S Sidhu, G A Alshafie
• Journal: Anticancer research (Anticancer Res) 1997 Sep-Oct Vol. 17 Issue 5A Pg. 3335-9 ISSN: 0250-7005 [Print] Greece
• PMID: 9413168 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glucuronates
• N-((4-hydroxyphenyl)retinamide)-O-glucuronide
• Fenretinide
• 9,10-Dimethyl-1,2-benzanthracene

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Body Weight (drug effects)
• Female
• Fenretinide (analogs & derivatives, pharmacology, therapeutic use)
• Glucuronates (pharmacology, therapeutic use)
• Mammary Neoplasms, Experimental (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Structure-Activity Relationship