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 language | English |
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Pages (from-to) | 693-698 |
Number of pages | 6 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 52 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2003 Nov |
Externally published | Yes |
Keywords
- Apoptosis
- Melanoma
- Vitamin C
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
- Cancer Research