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.
Highlights
Ascorbic acid (AA, Figure 1), known as vitamin C, is a vital nutrient for health
The findings suggest that 6-bOcta-ascorbic acid (AA)-2G is a potent candidate as an alternative drug to intravenous high-dose AA
It has been reported that 90% or more of AA-2G
Summary
Ascorbic acid (AA, Figure 1), known as vitamin C, is a vital nutrient for health. Recently, intravenous high-dose AA has been studied as a treatment for cancer patients [1,2,3,4]. Recently reported that high-dose intravenous well as AA significantly inhibited tumor after enzymatic hydrolysis to AA by α-glucosidase. We as recently reported that high-dose intravenous growth as in well tumor-bearing mice [17].inhibited. Expected to by be activity that of AA-2G was caused by reactive species that were generated byisAA released an alternative drug for intravenous that improves the instability of AA. Patientshigh-dose with renalAA failure cannot receive intravenous stable ascorbic acid derivatives that exert strong antitumor activity low doses that is important. Of the 6-sAcyl-AA-2G derivatives, activities ofactivities hyaluronidase and degranulation derivatives, 6-sPalm-AA-2G, 6-sPalm-AA-2G, having achain, C16 straight-acyl significantly suppressedanaphylaxis passive cutaneous having a C16 straight-acyl significantly chain, suppressed passive cutaneous reaction, anaphylaxis reaction, which is a model of type.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
