High-Dose Vitamin C Administration Inhibits the Invasion and Proliferation of Melanoma Cells in Mice Ovary

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 1; pp. 75 - 81
• Main Authors: Nakanishi, Kentaro, Hiramoto, Keiichi, Sato, Eisuke F, Ooi, Kazuya
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.01.2021; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Ascorbic acid; Cell proliferation; Dihydroxyphenylalanine; DNA nucleotidylexotransferase; Glycoprotein gp100; Hydrogen peroxide; Inflammation; Jejunum; Leukocytes (neutrophilic); Macrophage inflammatory protein; Melanoma; neutrophil; Neutrophils; Oral administration; Ovaries; ovary; Vitamin C; melanoma; ovary; vitamin C; neutrophil
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b20-00637

Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.