Abstract |
The antitumor effects of N-(4-hydroxyphenyl)retinamide (4-HPR), and its stable C-linked analog, 4-hydroxybenzylretinone (4-HBR) on the regression of established 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary tumors were compared. 4-HBR is a stable and nonhydroyzable derivative which cannot be converted in vivo to retinoic acid (RA). The results indicate that 4-HBR decreased mammary tumor volumes to the same extent as equimolar concentration (2 mmol/kg diet) of 4-HPR (-45% for 4-HBR vs. -42% for 4-HPR, p<0.01). Both 4-HPR and 4-HBR bind very poorly to nuclear retinoid receptors RARs and RXRs. The similarity of physicochemical properties of 4-HPR and 4-HBR as well as their equal antitumor potency suggests that 4-HPR like 4-HBR, is acting directly rather than through hydrolysis to free RA. Treatment with 4-HPR caused an almost 65% decrease in serum retinol levels. These results suggest that 4-HBR may have a significant chemotherapeutic advantage over 4-HPR, as the nonhydrolyzable analog may not cause night blindness which occurs as a significant side effect of 4-HPR usage.
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Authors | H Abou-Issa, R W Curley Jr, G A Alshafie, K L Weiss, M Clagett-Dame, J S Chapman, S M Mershon |
Journal | Anticancer research
(Anticancer Res)
2001 Nov-Dec
Vol. 21
Issue 6A
Pg. 3839-44
ISSN: 0250-7005 [Print] Greece |
PMID | 11911255
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- 4-hydroxybenzylretinone
- Anticarcinogenic Agents
- Antineoplastic Agents
- Carcinogens
- Receptors, Retinoic Acid
- Vitamin A
- Fenretinide
- 9,10-Dimethyl-1,2-benzanthracene
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Topics |
- 9,10-Dimethyl-1,2-benzanthracene
- Animals
- Anticarcinogenic Agents
(metabolism, pharmacology)
- Antineoplastic Agents
(metabolism, pharmacology)
- Carcinogens
- Female
- Fenretinide
(analogs & derivatives, metabolism, pharmacology)
- Mammary Neoplasms, Experimental
(chemically induced, drug therapy, metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Retinoic Acid
(metabolism)
- Vitamin A
(analogs & derivatives, blood, metabolism, pharmacology)
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