Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation.

Abstract

We previously reported the anti-inflammatory effects of cilostazol, a selective inhibitor of phosphodiesterase 3, and two antioxidants, enzymatically modified isoquercitrin and α-lipoic acid in a dextran sodium sulphate-induced colitis mouse model. We further examined the chemopreventive effects of these substances in a murine azoxymethane/dextran sodium sulphate -induced colorectal carcinoma model and compared the effects with those of the well-known anticancer natural plant pigment, anthocyanin. In addition, the effects on cell proliferation activity were evaluated in colon cancer cell lines and mucosal epithelial cells in a model of acute dextran sodium sulphate-induced colitis. Cilostazol and enzymatically modified isoquercitrin improved the outcome of azoxymethane/dextran sodium sulphate-induced colorectal cancer along with anthocyanin though inhibiting inflammation and cell proliferation, but the effect of α-lipoic acid was minimal. Inhibition of cell proliferation by cilostazol was confirmed in vitro. In the acute dextran sodium sulphate-induced colitis model, cilostazol and enzymatically modified isoquercitrin prevented the decrease in epithelial proliferative cells. These results indicate that cilostazol and enzymatically modified isoquercitrin first exhibited an anti-dextran sodium sulphate effect at the initial stage of colitis and then showed antitumour effects throughout subsequent inflammation-related cancer developmental stages.

• Authors: Yumi Kangawa, Toshinori Yoshida, Kiyoshi Maruyama, Minako Okamoto, Tohru Kihara, Michi Nakamura, Masako Ochiai, Yoshitaka Hippo, Shim-Mo Hayashi, Makoto Shibutani
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 100 Pg. 103-114 (Feb 2017) ISSN: 1873-6351 [Electronic] England
• PMID: 27989839 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Carcinogens
• Tetrazoles
• Vasodilator Agents
• isoquercitrin
• Quercetin
• Azoxymethane
• Cilostazol

Topics

• Animals
• Azoxymethane (toxicity)
• Carcinogens (toxicity)
• Cell Proliferation (drug effects)
• Cilostazol
• Colitis (chemically induced, drug therapy, pathology)
• Colonic Neoplasms (chemically induced, drug therapy, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunohistochemistry
• Inflammation (metabolism, prevention & control)
• Mice
• Mice, Inbred BALB C
• Organ Size (drug effects)
• Quercetin (analogs & derivatives, pharmacology)
• Tetrazoles (pharmacology)
• Vasodilator Agents (pharmacology)