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, Eunsil Hahm, Yoolhee Yang, Daejin Kim, Daeyoung Hur, Hyunjeong Park, Saic Bang, Young Il Hwang, Wang Jae Lee

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47 Citations (Scopus)


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
Pages (from-to)693-698
Number of pages6
JournalCancer Immunology, Immunotherapy
Issue number11
Publication statusPublished - 2003 Nov
Externally publishedYes


  • Apoptosis
  • Melanoma
  • Vitamin C

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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