Reference - Detail
| RRC ID | 52600 |
|---|---|
| Author | Miura K, Haraguchi M, Ito H, Tai A. |
| Title | Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid. |
| Journal | Int J Mol Sci |
| 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. |
| Volume | 19(2) |
| Published | 2018-2-10 |
| DOI | 10.3390/ijms19020535 |
| PII | ijms19020535 |
| PMID | 29439410 |
| PMC | PMC5855757 |
| MeSH | Animals Antineoplastic Agents / chemical synthesis Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / therapeutic use* Ascorbic Acid / analogs & derivatives* Ascorbic Acid / chemical synthesis Ascorbic Acid / pharmacokinetics Ascorbic Acid / therapeutic use* Cell Line, Tumor Female Glucosides / chemical synthesis Glucosides / pharmacokinetics Glucosides / therapeutic use* Mice Mice, Inbred BALB C Neoplasms, Experimental / drug therapy* Tissue Distribution |
| IF | 4.556 |
| Times Cited | 3 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Colon-26(RCB2657) |