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Int. J. Mol. Sci. 2018, 19(2), 535; https://doi.org/10.3390/ijms19020535

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

1
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan
2
Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan
*
Author to whom correspondence should be addressed.
Received: 18 January 2018 / Revised: 30 January 2018 / Accepted: 6 February 2018 / Published: 10 February 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
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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. View Full-Text
Keywords: ascorbic acid; stable ascorbic acid derivatives; acyl ascorbic acid; antitumor activity ascorbic acid; stable ascorbic acid derivatives; acyl ascorbic acid; antitumor activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Miura, K.; Haraguchi, M.; Ito, H.; Tai, A. Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid. Int. J. Mol. Sci. 2018, 19, 535.

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