Peroxisome proliferator-activated receptor gamma ligands suppress colon carcinogenesis induced by azoxymethane in mice.
OBJECTIVE
Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate growth arrest and terminal differentiation of adipocytes and is used clinically as a new class of antidiabetic drugs. Recently, several studies have reported that treatment of cancer cells with PPARgamma ligands induces cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. However, contradictory results have been reported with regards to the biologic role of PPARgamma in carcinogenesis. Tanaka et al.(24) have recently reported the suppressive effect of a PPARgamma ligand, troglitazone (Tro), on the formation of aberrant crypt foci (ACF) in rats. In the present study, 3 different kinds of PPARgamma ligands were subjected to the experiments to confirm their suppressive effects on colon carcinogenesis.


METHODS
Three PPARgamma ligands, pioglitazone (Pio) (200 ppm), rosiglitazone (Rosi) (200 ppm), and Tro (1000 ppm) were investigated on the induction of ACF, a putative precancerous lesion of the colon, and colon tumor formation using an azoxymethane (AOM)-induced colon cancer model in BALB/c mice, and dose dependency of a PPARgamma ligand was also examined.


RESULTS
PPARgamma ligands reduced the ACF formation by AOM (10 mg/kg body weight) and induction of colon tumors were also markedly suppressed by a continuous feeding of Pio at 200 ppm.


CONCLUSIONS
Our findings indicate that PPARgamma ligands are indeed potential chemopreventive agents for colon carcinogenesis.
Osawa
Emi
E
The Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Nakajima
Atsushi
A
Wada
Koichiro
K
Ishimine
Satoko
S
Fujisawa
Nobutaka
N
Kawamori
Toshihiko
T
Matsuhashi
Nobuyuki
N
Kadowaki
Takashi
T
Ochiai
Masako
M
Sekihara
Hisahiko
H
Nakagama
Hitoshi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D002273:Carcinogens; D002839:Chromans / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002273:Carcinogens; D002839:Chromans; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077288:Troglitazone; D001397:Azoxymethane; D000077205:Pioglitazone