Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice.

Abstract

Type 2 diabetes mellitus and its related insulin resistance are known to increase the risk of cancer. Anti-diabetic agents can improve insulin resistance and may lead to the suppression of carcinogenesis. This study aimed to investigate the preventive effects of the alpha-glucosidase inhibitor voglibose on the development of azoxymethane-induced colorectal pre-neoplastic lesions in obese and diabetic C57BL/KsJ-db/db mice. The direct effects of voglibose on the proliferation of colorectal cancer cells were also evaluated. Mice were injected with azoxymethane to induce colorectal pre-malignancy and were then administered drinking water with or without voglibose. At the end of the study, the administration of voglibose significantly suppressed the development of colorectal neoplastic lesions. In voglibose-treated mice, serum glucose levels, oxidative stress, as well as mRNA expression of the insulin-like growth factor-1 in the colon mucosa, were reduced. The proliferation of human colorectal cancer cells was not altered by voglibose. These results suggested that voglibose suppressed colorectal carcinogenesis in a diabetes- and obesity-related colorectal cancer model, presumably by improving inflammation via the reduction of oxidative stress and suppressing of the insulin-like growth factor/insulin-like growth factor-1 receptor axis in the colonic mucosa.

• Authors: Junichi Kato, Yohei Shirakami, Taku Mizutani, Masaya Kubota, Hiroyasu Sakai, Takashi Ibuka, Masahito Shimizu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 6 (Mar 23 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32210144 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Biomarkers
• Cytokines
• Glycoside Hydrolase Inhibitors
• Inflammation Mediators
• NF-kappa B
• Inositol
• Azoxymethane
• voglibose

Topics

• Animals
• Antioxidants (chemistry, pharmacology)
• Azoxymethane (adverse effects)
• Biomarkers
• Biopsy
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, etiology, pathology)
• Cytokines (metabolism)
• Diabetes Mellitus, Type 2 (complications, metabolism)
• Disease Models, Animal
• Glycoside Hydrolase Inhibitors (chemistry, pharmacology)
• Humans
• Inflammation Mediators
• Inositol (analogs & derivatives, chemistry, pharmacology)
• Intestinal Mucosa (drug effects, metabolism, pathology)
• Mice
• NF-kappa B (metabolism)
• Obesity (complications, metabolism)
• Oxidative Stress (drug effects)
• Precancerous Conditions