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Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake

Cited 40 time in Web of Science Cited 44 time in Scopus
Authors
KANG, JAE SEUNG; CHO, DAEHO; KIM, YOUNG-IN; HAHM, EUNSIL; KIM, YEONG SEOK; JIN, SHUN NU; KIM, HA NA; KIM, DAEJIN.; HUR, DAEYOUNG; PARK, HYUNJEONG; HWANG, YOUNG IL; LEE, WANG JAE
Issue Date
2005
Publisher
Wiley-Blackwell
Citation
J Cell Physiol 204:192-197
Keywords
AnimalsAntioxidants/*pharmacologyApoptosis/drug effectsAscorbic Acid/*pharmacologyCell Line, TumorDown-Regulation/drug effectsGene Expression Regulation, Neoplastic/drug effectsIron/*pharmacokineticsMelanoma/*drug therapy/metabolism/physiopathologyMiceRNA Processing, Post-Transcriptional/drug effectsReceptors, Transferrin/*genetics/metabolismSkin Neoplasms/*drug therapy/metabolism/physiopathology
Abstract
Sodium ascorbate (vitamin C) has a reputation for inconsistent effects upon malignant tumor cells, which vary from growth stimulation to apoptosis induction. Melanoma cells were found to be more susceptible to vitamin C toxicity than any other tumor cells. The present study has shown that sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose- and time-dependent fashion, indicating that intracellular iron levels may be a critical factor in sodium ascorbate-induced apoptosis. Indeed, sodium ascorbate-induced apoptosis is enhanced by the iron chelator, desferrioxamine (DFO) while it is inhibited by the iron donor, ferric ammonium citrate (FAC). Moreover, the inhibitory effects of sodium ascorbate on intracellular iron levels are blocked by addition of transferrin, suggesting that transferrin receptor (TfR) dependent pathway of iron uptake may be regulated by sodium ascorbate. Cells exposed to sodium ascorbate demonstrated down-regulation of TfR expression and this precedes sodium ascorbate-induced apoptosis. Taken together, sodium ascorbate-mediated apoptosis appears to be initiated by a reduction of TfR expression, resulting in a down-regulation of iron uptake followed by an induction of apoptosis. This study demonstrates the specific mechanism of sodium ascorbate-induced apoptosis and these findings support future clinical trial of sodium ascorbate in the prevention of human melanoma relapse.
ISSN
0021-9541 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15672419

http://hdl.handle.net/10371/28285
DOI
https://doi.org/10.1002/jcp.20286
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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