High-Dose Vitamin C Exerts Its Anti-cancer Effects in a Xenograft Model of Colon Cancer by Suppressing Angiogenesis

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 6; pp. 884 - 887
• Main Authors: Nakanishi, Kentaro, Hiramoto, Keiichi, Ooi, Kazuya
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.06.2021; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Angiogenesis; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Ascorbic acid; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Cancer; Cell Line, Tumor; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Dosage; Endostatin; Endostatins - metabolism; Heterografts; hypoxia inducible factor-1α (HIF-1α); Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Male; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Oral administration; p53 Protein; Reactive oxygen species; reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Rectum; Tumor Suppressor Protein p53 - metabolism; Tumors; Vascular endothelial growth factor; vascular endothelial growth factor (VEGF); Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor D; Vascular Endothelial Growth Factor D - metabolism; Vitamin C; Vitamins - pharmacology; Vitamins - therapeutic use; Xenografts; hypoxia inducible factor-1α (HIF-1α); vascular endothelial growth factor (VEGF); reactive oxygen species (ROS); endostatin; vitamin C
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00089

Several studies have been conducted to investigate the anti-cancer effects of vitamin C (VC). However, the effect of high-dose VC administration on tumor angiogenesis remains unclear. Focusing on our high-dose VC, our study investigated the effect of high-dose VC (4 g/kg) on vascular endothelial growth in mice with xenografts of a rectal cancer cell line referred to as Colon 26. Male mice harboring Colon 26 tumors were established, and high-dose VC solution was orally administered once daily for 14 d. On the final day of the study, the lower limb tumor tissues and serum samples were collected and analyzed for the expression of tumor angiogenesis related proteins as well as the levels of reactive oxygen species (ROS). Oral VC administration decreased tumor volumes and increased p53 and endostatin levels. In addition, plasma and in tumor part ROS levels and tissue hypoxia inducible factor-1α (HIF-1α) were reduced by VC administration. In addition, the levels of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor D (VEGFD) were decreased by VC administration. These results suggest that VC exerts its anti-cancer effects by suppressing angiogenesis.