NO-donating aspirin inhibits intestinal carcinogenesis in Min (APC(Min/+)) mice.
The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against gastrointestinal tumorigenesis was evaluated in Min (APC(Min/+)) mice. NO-ASA consists of a traditional ASA that bears covalently attached to it an NO-releasing moiety. Four groups (N=10) of six-week-old female C57BL/6J APC(Min/+) and the corresponding C57BL/6J(+/+) wild type mice were treated either with vehicle or NO-ASA 100 mg/kg/day intrarectally for 21 days. There were no signs of overt toxicity including gastrointestinal toxicity from NO-ASA. Vehicle treated Min mice had 24.7 +/- 3.8 tumors (mean +/- SEM) and NO-ASA treated Min mice had 10.1 +/- 1.4 tumors (59% reduction; P<0.001). Wild type mice showed no tumors. NO-ASA did not affect cell proliferation in small intestinal mucosa, determined by immunohistochemical staining for PCNA. Our findings establish the strong inhibitory effect of NO-ASA in intestinal carcinogenesis in the Min mouse and suggest that this agent merits further evaluation as a chemopreventive agent against colon cancer.
Williams
Jennie L
JL
American Health Foundation Cancer Center, Institute for Cancer Prevention, Valhalla, NY 06595, USA.
Kashfi
Khosrow
K
Ouyang
Nengtai
N
del Soldato
Piero
P
Kopelovich
Levy
L
Rigas
Basil
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001835:Body Weight; D002455:Cell Division; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000517:prevention & control*; D017491:Genes, APC; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D018809:Proliferating Cell Nuclear Antigen; D009569:Nitric Oxide; D001241:Aspirin