Chemotherapeutic evaluation of N-(4-hydroxyphenyl) retinamide-O-glucuronide in the rat mammary tumor model.
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.
Abou-Issa
H
H
Department of Surgery, College of Medicine, Ohio State University, Columbus 43210, USA.
Curley
R W
RW
Panigot
M J
MJ
Tanagho
S N
SN
Sidhu
B S
BS
Alshafie
G A
GA
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D017313:Fenretinide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D005965:Glucuronates / Q000494:pharmacology / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D005965:Glucuronates; C084238:N-((4-hydroxyphenyl)retinamide)-O-glucuronide; D017313:Fenretinide; D015127:9,10-Dimethyl-1,2-benzanthracene