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 Kang
  • Daeho Cho
  • Young-In Kim
  • Eunsil Hahm
  • Yoolhee Yang
  • Daejin Kim
  • Daeyoung Hur
  • Hyunjeong Park
  • Saic Bang
  • Young Il Hwang
  • Wang Jae Lee
Original Article

DOI: 10.1007/s00262-003-0407-6

Cite this article as:
Kang, J.S., Cho, D., Kim, YI. et al. Cancer Immunol Immunother (2003) 52: 693. doi:10.1007/s00262-003-0407-6

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 CMelanomaApoptosis

Abbreviations

NAC

N-acetyl-l-cysteine

ROS

reactive oxygen species

Δψm

mitochondrial membrane potential

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Jae Seung Kang
    • 1
  • Daeho Cho
    • 2
  • Young-In Kim
    • 1
  • Eunsil Hahm
    • 1
  • Yoolhee Yang
    • 2
  • Daejin Kim
    • 1
  • Daeyoung Hur
    • 3
  • Hyunjeong Park
    • 4
  • Saic Bang
    • 5
  • Young Il Hwang
    • 1
  • Wang Jae Lee
    • 6
  1. 1.Department of Anatomy and Tumor Immunity Medical Research CenterSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Life ScienceSookmyung Women's UniversitySeoulSouth Korea
  3. 3.Department of AnatomyInje University College of MedicinePusanSouth Korea
  4. 4.Department of Dermatology, St. Mary's HospitalThe Catholic University of KoreaPuchonSouth Korea
  5. 5.Department of Plastic Surgery, College of MedicineSungkyunkwan UniversitySeoulSouth Korea
  6. 6.Department of AnatomySeoul National University College of MedicineSeoulSouth Korea