Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice.

Abstract

Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model.

• Authors: Kazufumi Fukuta, Yohei Shirakami, Akinori Maruta, Koki Obara, Soichi Iritani, Nobuhiko Nakamura, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 2 (Feb 15 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28212276 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Biomarkers
• Cytokines
• Inflammation Mediators
• beta Catenin
• Cyclooxygenase 2
• Pentoxifylline

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Biomarkers
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Chemoprevention
• Colonic Neoplasms (etiology, metabolism, pathology, prevention & control)
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokines (genetics, metabolism)
• Diabetes Mellitus, Experimental
• Disease Models, Animal
• Gene Expression
• Inflammation Mediators (metabolism)
• Intestinal Mucosa (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (complications, metabolism)
• Oxidative Stress (drug effects)
• Pentoxifylline (pharmacology)
• Precancerous Conditions
• beta Catenin (metabolism)