Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands.
The objective of this study was to evaluate the ability of troglitazone (a thiazolidinedione) and Wy-14,643 (a clofibrate) to inhibit progression of non-detectable and detectable mammary tumors in rats induced by 7,12 dimethylbenz(a)anthracene (DMBA) when compared to those receiving no treatment or tamoxifen. Although not as effective as tamoxifen in decreasing overall tumor incidence, Wy-14,643 reduced the percentage and number of malignant tumors that developed when compared to both troglitazone and control. Treatment of detectable tumors with either Wy-14,643 or troglitazone induced regression or stasis of total tumor volume in 40-50% of the animals, compared to only 10% in control and 65% in tamoxifen treated animals. Moreover, each PPAR ligand was as effective as tamoxifen in preventing additional tumor development. In summary, both PPAR ligands were more effective than no treatment in preventing tumor progression once detected. However, only the PPAR-alpha activator, Wy-14,643 was able to reduce the development of malignant tumors when administered prior to detection.
Pighetti
G M
GM
Department of Dairy and Animal Science, University of Tennessee, 114B McCord, 2640 Morgan Circle Drive, Knoxville, TN 37996, USA. gpighetti@utk.edu
Novosad
W
W
Nicholson
C
C
Hitt
D C
DC
Hansens
C
C
Hollingsworth
A B
AB
Lerner
M L
ML
Brackett
D
D
Lightfoot
S A
SA
Gimble
J M
JM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D002784:Cholesterol / Q000378:metabolism; D002839:Chromans / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D008024:Ligands; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020025:Peroxisome Proliferators / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D000077288:Troglitazone
D000924:Anticholesteremic Agents; D000970:Antineoplastic Agents; D002273:Carcinogens; D002839:Chromans; D008024:Ligands; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014280:Triglycerides; D015127:9,10-Dimethyl-1,2-benzanthracene; C006253:pirinixic acid; D002784:Cholesterol; D000077288:Troglitazone