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

Jae Seung Kang, Dae Ho Cho, Young In Kim, Eunsil Hahm, Yeong Seok Kim, Shun Nu Jin, Ha Na Kim, Daejin Kim, Daeyoung Hur, Hyunjeong Park, Young Il Hwang, Wang Jae Lee

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalJournal of Cellular Physiology
Volume204
Issue number1
DOIs
Publication statusPublished - 2005 Jul 1
Externally publishedYes

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Transferrin Receptors
Ascorbic Acid
Melanoma
Down-Regulation
Iron
Apoptosis
Tumors
Cells
Deferoxamine
Transferrin
Chelating Agents
Toxicity
Neoplasms

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake. / Kang, Jae Seung; Cho, Dae Ho; 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.

In: Journal of Cellular Physiology, Vol. 204, No. 1, 01.07.2005, p. 192-197.

Research output: Contribution to journalArticle

Kang, JS, Cho, DH, Kim, YI, Hahm, E, Kim, YS, Jin, SN, Kim, HN, Kim, D, Hur, D, Park, H, Hwang, YI & Lee, WJ 2005, 'Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake', Journal of Cellular Physiology, vol. 204, no. 1, pp. 192-197. https://doi.org/10.1002/jcp.20286
Kang, Jae Seung ; Cho, Dae Ho ; 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. / Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake. In: Journal of Cellular Physiology. 2005 ; Vol. 204, No. 1. pp. 192-197.
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