Mechanistic studies on the inhibitory action of dietary dibenzoylmethane, a beta-diketone analogue of curcumin, on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis.
Dietary factors play important roles in the carcinogenic process. The results of epidemiological data and some laboratory animal studies indicate that certain naturally occurring and synthetic components are able to block the carcinogenic process and inhibit the development of certain cancers. Dibenzoylmethane (DBM), a curcumin-related beta-diketone analogue has been reported to exhibit a remarkable inhibitory effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in Sencar mice. The present study investigated the possible mechanisms of inhibitory action of DBM on DMBA-induced mammary tumorigenesis in mice. The summarized results indicate that: (1) in in-vitro studies. DBM inhibited DMBA metabolism and the formation of DMBA-DNA adducts in a dose-dependent manner; (2) in the assay of competitive binding to estrogen receptors with [3H]-estradiol in vitro, DBM showed weak binding affinity; (3) in vivo, feeding of 1% DBM in the diet of immature Sencar mice for 4 -5 weeks decreased the uterine and parametrial fat pad weights, and lowered the serum estrogen and triglyceride levels. This study provides insight into the mechanisms involved in the inhibitory action of DBM in mouse mammary tumorigenesis.
Lin
C C
CC
Laboratory for Cancer Research, College of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, USA.
Ho
C T
CT
Huang
M T
MT
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D001667:Binding, Competitive; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity; D002417:Cattle; D047188:Chalcones; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D004041:Dietary Fats / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D018632:Mice, Inbred SENCAR; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D017365:Spices; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000737:chemistry
D016588:Anticarcinogenic Agents; D001565:Benzoates; D002273:Carcinogens; D047188:Chalcones; D018736:DNA Adducts; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D011960:Receptors, Estrogen; D014280:Triglycerides; D011374:Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; C061481:dibenzoylmethane; D003474:Curcumin