Original Article

Cancer Immunology, Immunotherapy

, Volume 52, Issue 11, pp 693-698

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

  • Jae Seung KangAffiliated withDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine
  • , Daeho ChoAffiliated withDepartment of Life Science, Sookmyung Women's University
  • , Young-In KimAffiliated withDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine
  • , Eunsil HahmAffiliated withDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine
  • , Yoolhee YangAffiliated withDepartment of Life Science, Sookmyung Women's University
  • , Daejin KimAffiliated withDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine
  • , Daeyoung HurAffiliated withDepartment of Anatomy, Inje University College of Medicine
  • , Hyunjeong ParkAffiliated withDepartment of Dermatology, St. Mary's Hospital, The Catholic University of Korea
  • , Saic BangAffiliated withDepartment of Plastic Surgery, College of Medicine, Sungkyunkwan University
    • , Young Il HwangAffiliated withDepartment of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine
    • , Wang Jae LeeAffiliated withDepartment of Anatomy, Seoul National University College of Medicine Email author 

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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.

Keywords

Vitamin C Melanoma Apoptosis