Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
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...
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doaj-cb5c71c014284dc1b50bb6d5e86ea7722020-11-24T21:06:33ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-02-0118241310.3390/ijms18020413ijms18020413Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic MiceKazufumi Fukuta0Yohei Shirakami1Akinori Maruta2Koki Obara3Soichi Iritani4Nobuhiko Nakamura5Takahiro Kochi6Masaya Kubota7Hiroyasu Sakai8Takuji Tanaka9Masahito Shimizu10Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pathological Diagnosis, Gifu Municipal Hospital, Gifu 500-8513, JapanDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanObesity 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.http://www.mdpi.com/1422-0067/18/2/413colorectal cancerpentoxifyllinechemopreventionobesityoxidative stressinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kazufumi Fukuta Yohei Shirakami Akinori Maruta Koki Obara Soichi Iritani Nobuhiko Nakamura Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takuji Tanaka Masahito Shimizu |
spellingShingle |
Kazufumi Fukuta Yohei Shirakami Akinori Maruta Koki Obara Soichi Iritani Nobuhiko Nakamura Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takuji Tanaka Masahito Shimizu Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice International Journal of Molecular Sciences colorectal cancer pentoxifylline chemoprevention obesity oxidative stress inflammation |
author_facet |
Kazufumi Fukuta Yohei Shirakami Akinori Maruta Koki Obara Soichi Iritani Nobuhiko Nakamura Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takuji Tanaka Masahito Shimizu |
author_sort |
Kazufumi Fukuta |
title |
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice |
title_short |
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice |
title_full |
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice |
title_fullStr |
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice |
title_full_unstemmed |
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice |
title_sort |
preventive effects of pentoxifylline on the development of colonic premalignant lesions in obese and diabetic mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-02-01 |
description |
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. |
topic |
colorectal cancer pentoxifylline chemoprevention obesity oxidative stress inflammation |
url |
http://www.mdpi.com/1422-0067/18/2/413 |
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