2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy
Ascorbic acid (AA) has been reported as a treatment for cancer patients. Intravenous (iv) administration of high-dose AA increases plasma AA levels to pharmacologic concentrations and generates reactive oxygen species (ROS) to exert anti-tumor activity via enhancement of oxidative stress. However, A...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240558081630259X |
| _version_ | 1811344324638539776 |
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| author | Kaori Miura Akihiro Tai |
| author_facet | Kaori Miura Akihiro Tai |
| author_sort | Kaori Miura |
| collection | DOAJ |
| description | Ascorbic acid (AA) has been reported as a treatment for cancer patients. Intravenous (iv) administration of high-dose AA increases plasma AA levels to pharmacologic concentrations and generates reactive oxygen species (ROS) to exert anti-tumor activity via enhancement of oxidative stress. However, AA is very unstable in aqueous solutions and it is impossible to preserve AA for a long period in a solution. 2-O-α-D-Glucopyranosyl-l-ascorbic acid (AA-2G), which is a glucoside derivative of AA, has been found to exhibit much higher stability than AA in aqueous solutions and it shows vitamin C activity after enzymatic hydrolysis to AA. To evaluate the effectiveness of AA-2G for cancer treatment, we examined the antitumor activity of AA-2G to murine colon carcinoma (colon-26) cells and in tumor-bearing mice. AA-2G did not show cytotoxicity to colon-26 cells, whereas AA exhibited a significant cytotoxic effect in a concentration-dependent manner. In colon-26 tumor-bearing mice, iv administration of high-dose AA-2G as well as that of AA significantly inhibited tumor growth. Experiments on the biodistribution and clearance of AA-2G in tumor-bearing mice showed that AA-2G was rapidly hydrolyzed to AA and exhibited significant antitumor activity. Treatment of tumor-bearing mice with AA-2G tended to increase plasma malondialdehyde level. These results indicated that the antitumor activity of AA-2G was caused by ROS generated by AA released by rapid hydrolysis of AA-2G. |
| first_indexed | 2024-04-13T19:45:39Z |
| format | Article |
| id | doaj.art-abfdf93110d940bd874fd4b5700a9b39 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-04-13T19:45:39Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-abfdf93110d940bd874fd4b5700a9b392022-12-22T02:32:45ZengElsevierBiochemistry and Biophysics Reports2405-58082017-07-0110C23223610.1016/j.bbrep.2017.04.0142-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapyKaori MiuraAkihiro TaiAscorbic acid (AA) has been reported as a treatment for cancer patients. Intravenous (iv) administration of high-dose AA increases plasma AA levels to pharmacologic concentrations and generates reactive oxygen species (ROS) to exert anti-tumor activity via enhancement of oxidative stress. However, AA is very unstable in aqueous solutions and it is impossible to preserve AA for a long period in a solution. 2-O-α-D-Glucopyranosyl-l-ascorbic acid (AA-2G), which is a glucoside derivative of AA, has been found to exhibit much higher stability than AA in aqueous solutions and it shows vitamin C activity after enzymatic hydrolysis to AA. To evaluate the effectiveness of AA-2G for cancer treatment, we examined the antitumor activity of AA-2G to murine colon carcinoma (colon-26) cells and in tumor-bearing mice. AA-2G did not show cytotoxicity to colon-26 cells, whereas AA exhibited a significant cytotoxic effect in a concentration-dependent manner. In colon-26 tumor-bearing mice, iv administration of high-dose AA-2G as well as that of AA significantly inhibited tumor growth. Experiments on the biodistribution and clearance of AA-2G in tumor-bearing mice showed that AA-2G was rapidly hydrolyzed to AA and exhibited significant antitumor activity. Treatment of tumor-bearing mice with AA-2G tended to increase plasma malondialdehyde level. These results indicated that the antitumor activity of AA-2G was caused by ROS generated by AA released by rapid hydrolysis of AA-2G.http://www.sciencedirect.com/science/article/pii/S240558081630259X2-O-α-D-glucopyranosyl-L-ascorbic acidAscorbic acidCancerOxidative stress |
| spellingShingle | Kaori Miura Akihiro Tai 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy Biochemistry and Biophysics Reports 2-O-α-D-glucopyranosyl-L-ascorbic acid Ascorbic acid Cancer Oxidative stress |
| title | 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy |
| title_full | 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy |
| title_fullStr | 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy |
| title_full_unstemmed | 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy |
| title_short | 2-O-α-D-Glucopyranosyl-l-ascorbic acid as an antitumor agent for infusion therapy |
| title_sort | 2 o α d glucopyranosyl l ascorbic acid as an antitumor agent for infusion therapy |
| topic | 2-O-α-D-glucopyranosyl-L-ascorbic acid Ascorbic acid Cancer Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S240558081630259X |
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