| The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. | |
| | |
MedLine Citation:
|
PMID: 20213077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: Ascorbic acid is an essential micronutrient and is considered to have an antioxidant function in living systems. For the past several decades, ascorbic acid has been the subject of considerable interest as an anticancer agent. Several studies have shown that ascorbic acid is cytotoxic to a variety of cancer cells, whereas normal cells are relatively resistant to such cytotoxic action. In this study, we propose a putative molecular mechanism that accounts for the preferential cytotoxicity of ascorbic acid against cancer cells. METHODS: Standard and lysed version of alkaline single-cell gel electrophoresis (Comet assay); ferrous oxidation-xylenol orange (FOX) assay. RESULTS: We show that ascorbic acid acts as a prooxidant and leads to oxidative DNA breakage in lymphocytes and lymphocyte nuclei. Scavengers of reactive oxygen species were able to inhibit ascorbic acid-induced DNA breakage, suggesting the involvement of reactive oxygen species in this reaction. We further show that such DNA breakage is inhibited by both iron and copper chelators in cells, whereas in nuclei, similar inhibition was achieved only by copper chelators, indicating an important role of chromatin-bound copper in the prooxidant cellular DNA breakage by ascorbic acid. CONCLUSION: We propose that the copper-dependent cellular redox status is an important element in the cytotoxic action of ascorbic acid against cancer cells. It is well established that cellular copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper and ascorbate to generate reactive oxygen species. In light of these observations and those in literature, in this paper we explain that the preferential cytotoxicity of ascorbic acid against cancer cells is the result of elevated copper levels in such cells. Further, this study identifies nuclear copper as a novel molecular target for cytotoxic action of ascorbic acid, which has implications for its chemotherapeutic properties against cancer. |
| | |
Authors:
|
M F Ullah; H Y Khan; H Zubair; U Shamim; S M Hadi |
Related Documents
:
|
10468217 - Antioxidant protection from solar-simulated radiation-induced suppression of contact hy... 3677097 - Inhibition of 12-o-tetradecanoylphorbol-13-acetate induction of ornithine decarboxylase... 11809377 - Antioxidant inhibition of porphyrin-induced cellular phototoxicity. 16822727 - An isocratic hplc method for the simultaneous determination of novel stable lipophilic ... 8437437 - Folic acid and vitamin b12 status of vervet monkeys used for nutritional research. 21878557 - A metabonomic characterization of (+)-usnic acid-induced liver injury by gas chromatogr... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-06 |
Journal Detail:
|
Title: Cancer chemotherapy and pharmacology Volume: 67 ISSN: 1432-0843 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-01-03 Completed Date: 2011-01-31 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
|
Languages: eng Pagination: 103-10 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, UP 202002, India. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antioxidants
/
pharmacology* Ascorbic Acid / pharmacology* Cell Nucleus / metabolism Comet Assay Copper / metabolism* DNA Breaks / drug effects* Drug Delivery Systems Humans Lymphocytes / drug effects*, metabolism Oxidation-Reduction Reactive Oxygen Species / metabolism Xylenes / chemistry |
| Chemical | |
Reg. No./Substance:
|
0/Antioxidants; 0/Reactive Oxygen Species; 0/Xylenes; 1611-35-4/xylenol orange; 50-81-7/Ascorbic Acid; 7440-50-8/Copper |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ruthenium-based chemotherapeutics: are they ready for prime time?
Next Document: Phase I study of intraperitoneal irinotecan in patients with gastric adenocarcinoma with peritoneal ...