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Int J Mol Sci. 2018 Feb 10;19(2). pii: E535. doi: 10.3390/ijms19020535.

Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid.

Author information

1
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. q531005dd@ed.pu-hiroshima.ac.jp.
2
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. q405088xe@ed.pu-hiroshima.ac.jp.
3
Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan. hito@fhw.oka-pu.ac.jp.
4
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. atai@pu-hiroshima.ac.jp.

Abstract

Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2-O-α-d-glucopyranosyl-6-O-(2-pentylheptanoyl)-l-ascorbic acid (6-bOcta-AA-2G). Intravenous administration of 6-bOcta-AA-2G suppressed tumor growth in colon-26 tumor-bearing mice more strongly than did AA, even at 1/10 of the molar amount of AA. Experiments on the biodistribution and clearance of 6-bOcta-AA-2G and its metabolites in tumor-bearing mice showed that 6-bOcta-AA-2G was hydrolyzed to 6-O-(2-propylpentanoyl)-l-ascorbic acid (6-bOcta-AA) slowly to yield AA, and the results suggested that this characteristic metabolic pattern is responsible for making the antitumor activity of 6-bOcta-AA-2G stronger than that of AA and that the active form of 6-bOcta-AA-2G showing antitumor activity is 6-bOcta-AA. In in vitro experiments, the oxidized form of 6-bOcta-AA as well as 6-bOcta-AA showed significant cytotoxicity, while the oxidized forms of ascorbic acid showed no cytotoxicity at all, suggesting that the antitumor activity mechanism of 6-bOcta-AA-2G is different from that of AA and that the antitumor activity is due to the reduced and oxidized form of 6-bOcta-AA. The findings suggest that 6-bOcta-AA-2G is a potent candidate as an alternative drug to intravenous high-dose AA.

KEYWORDS:

acyl ascorbic acid; antitumor activity; ascorbic acid; stable ascorbic acid derivatives

PMID:
29439410
PMCID:
PMC5855757
DOI:
10.3390/ijms19020535
[Indexed for MEDLINE]
Free PMC Article

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