L-Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway

Jae Seung Kang, Daeho Cho, Young In Kim Hoehamer, Eunsil Hahm, Yoolhee Yang, Daejin Kim, Daeyoung Hur, Hyunjeong Park, Saic Bang, Young Il Hwang, Wang Jae Lee

Research output: Contribution to journalArticle

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Abstract

L-Ascorbic acid (vitamin C) has been reported to play a role in the treatment and prevention of cancer. However, its specific mechanistic pathways remain obscure. This study was carried out to identify the sodium ascorbate-induced apoptotic pathway in B16F10 murine melanoma cells. Sodium ascorbate was found to induce the apoptosis of B16F10 murine melanoma in a time-and dose-dependent manner, and this was prevented by pretreatment with N-acetyl-L-cysteine (NAC), a well-known antioxidant. In fact, sodium ascorbate-treated B16F10 melanoma cells showed increased intracellular reactive oxygen species generation (ROS) levels. These results indicate that sodium ascorbate induced apoptosis in B16F10 murine melanoma cells by acting as a prooxidant. We examined the involvement of caspase-8 using a specific caspase-8 inhibitor (z-IETD-fmk) on the sodium ascorbate-induced apoptotic pathway. Cell death was found not to be inhibited by z-IETD-fmk treatment, indicating that sodium ascorbate-induced apoptosis is not mediated by caspase-8. In addition, we detected a reduction in the mitochondrial membrane potential during apoptosis and confirmed cytochrome-c release from mitochondria by immunoblotting. Taken together, it appears that the induction of a prooxidant state by sodium ascorbate and a subsequent reduction in mitochondrial membrane potential are involved in the apoptotic pathway of B16F10 murine melanoma cells, and that this occurs in a caspase-8-independent manner.

Original languageEnglish (US)
Pages (from-to)693-698
Number of pages6
JournalCancer Immunology, Immunotherapy
Volume52
Issue number11
DOIs
StatePublished - Nov 1 2003

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Experimental Melanomas
Caspase 8
Ascorbic Acid
Apoptosis
Melanoma
Mitochondrial Membrane Potential
Caspase Inhibitors
Acetylcysteine
Cytochromes c
Immunoblotting
Reactive Oxygen Species
Mitochondria
Cell Death
Antioxidants

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

L-Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway. / Kang, Jae Seung; Cho, Daeho; Kim Hoehamer, Young In; Hahm, Eunsil; Yang, Yoolhee; Kim, Daejin; Hur, Daeyoung; Park, Hyunjeong; Bang, Saic; Hwang, Young Il; Lee, Wang Jae.

In: Cancer Immunology, Immunotherapy, Vol. 52, No. 11, 01.11.2003, p. 693-698.

Research output: Contribution to journalArticle

Kang, JS, Cho, D, Kim Hoehamer, YI, Hahm, E, Yang, Y, Kim, D, Hur, D, Park, H, Bang, S, Hwang, YI & Lee, WJ 2003, 'L-Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway', Cancer Immunology, Immunotherapy, vol. 52, no. 11, pp. 693-698. https://doi.org/10.1007/s00262-003-0407-6
Kang, Jae Seung ; Cho, Daeho ; Kim Hoehamer, Young In ; Hahm, Eunsil ; Yang, Yoolhee ; Kim, Daejin ; Hur, Daeyoung ; Park, Hyunjeong ; Bang, Saic ; Hwang, Young Il ; Lee, Wang Jae. / L-Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway. In: Cancer Immunology, Immunotherapy. 2003 ; Vol. 52, No. 11. pp. 693-698.
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AU - Hahm, Eunsil

AU - Yang, Yoolhee

AU - Kim, Daejin

AU - Hur, Daeyoung

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