Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model
Angiogenesis requires the deposition of type IV collagen by endothelial cells into the basement membrane of new blood vessels. Stabilization of type IV collagen triple helix depends on the hydroxylation of proline, which is catalyzed by the iron-containing enzyme prolyl hydroxylase. This enzyme, in...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607800145 |
| _version_ | 1819140675006889984 |
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| author | Sucheta Telang Amy L. Clem John W. Eaton Jason Chesney |
| author_facet | Sucheta Telang Amy L. Clem John W. Eaton Jason Chesney |
| author_sort | Sucheta Telang |
| collection | DOAJ |
| description | Angiogenesis requires the deposition of type IV collagen by endothelial cells into the basement membrane of new blood vessels. Stabilization of type IV collagen triple helix depends on the hydroxylation of proline, which is catalyzed by the iron-containing enzyme prolyl hydroxylase. This enzyme, in turn, requires ascorbic acid to maintain the enzyme-bound iron in its reduced state. We hypothesized that dietary ascorbic acid might be required for tumor angiogenesis and, therefore, tumor growth. Here, we show that, not surprisingly, ascorbic acid is necessary for the synthesis of collagen type IV by human endothelial cells and for their effective migration and tube formation on a basement membrane matrix. Furthermore, ascorbic acid depletion in mice incapable of synthesizing ascorbic acid (Gulo-/-) dramatically restricts the in vivo growth of implanted Lewis lung carcinoma tumors. Histopathological analyses of these tumors reveal poorly formed blood vessels, extensive hemorrhagic foci, and decreased collagen and von Willebrand factor expression. Our data indicate that ascorbic acid plays an essential role in tumor angiogenesis and growth, and that restriction of ascorbic acid or pharmacological inhibition of prolyl hydroxylase may prove to be novel therapeutic approaches to the treatment of cancer. |
| first_indexed | 2024-12-22T11:42:19Z |
| format | Article |
| id | doaj.art-ba6a96eb8a5d4957ad8db90d2a17fde9 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-22T11:42:19Z |
| publishDate | 2007-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-ba6a96eb8a5d4957ad8db90d2a17fde92022-12-21T18:27:14ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-01-0191475610.1593/neo.06664Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse ModelSucheta TelangAmy L. ClemJohn W. EatonJason ChesneyAngiogenesis requires the deposition of type IV collagen by endothelial cells into the basement membrane of new blood vessels. Stabilization of type IV collagen triple helix depends on the hydroxylation of proline, which is catalyzed by the iron-containing enzyme prolyl hydroxylase. This enzyme, in turn, requires ascorbic acid to maintain the enzyme-bound iron in its reduced state. We hypothesized that dietary ascorbic acid might be required for tumor angiogenesis and, therefore, tumor growth. Here, we show that, not surprisingly, ascorbic acid is necessary for the synthesis of collagen type IV by human endothelial cells and for their effective migration and tube formation on a basement membrane matrix. Furthermore, ascorbic acid depletion in mice incapable of synthesizing ascorbic acid (Gulo-/-) dramatically restricts the in vivo growth of implanted Lewis lung carcinoma tumors. Histopathological analyses of these tumors reveal poorly formed blood vessels, extensive hemorrhagic foci, and decreased collagen and von Willebrand factor expression. Our data indicate that ascorbic acid plays an essential role in tumor angiogenesis and growth, and that restriction of ascorbic acid or pharmacological inhibition of prolyl hydroxylase may prove to be novel therapeutic approaches to the treatment of cancer.http://www.sciencedirect.com/science/article/pii/S1476558607800145Ascorbic acidtumorangiogenesiscollagenprolyl hydroxylase |
| spellingShingle | Sucheta Telang Amy L. Clem John W. Eaton Jason Chesney Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model Neoplasia: An International Journal for Oncology Research Ascorbic acid tumor angiogenesis collagen prolyl hydroxylase |
| title | Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model |
| title_full | Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model |
| title_fullStr | Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model |
| title_full_unstemmed | Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model |
| title_short | Depletion of Ascorbic Acid Restricts Angiogenesis and Retards Tumor Growth in a Mouse Model |
| title_sort | depletion of ascorbic acid restricts angiogenesis and retards tumor growth in a mouse model |
| topic | Ascorbic acid tumor angiogenesis collagen prolyl hydroxylase |
| url | http://www.sciencedirect.com/science/article/pii/S1476558607800145 |
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