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 |
|---|---|
| Pages (from-to) | 693-698 |
| Number of pages | 6 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 52 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2003 Nov 1 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Melanoma
- Vitamin C
ASJC Scopus subject areas
- 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, Dae Ho; Kim, 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 journal › Article
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TY - JOUR
T1 - L-Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway
AU - Kang, Jae Seung
AU - Cho, Dae Ho
AU - Kim, Young In
AU - Hahm, Eunsil
AU - Yang, Yoolhee
AU - Kim, Daejin
AU - Hur, Daeyoung
AU - Park, Hyunjeong
AU - Bang, Saic
AU - Hwang, Young Il
AU - Lee, Wang Jae
PY - 2003/11/1
Y1 - 2003/11/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Melanoma
KW - Vitamin C
UR - http://www.scopus.com/inward/record.url?scp=0242329380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242329380&partnerID=8YFLogxK
U2 - 10.1007/s00262-003-0407-6
DO - 10.1007/s00262-003-0407-6
M3 - Article
C2 - 12827307
AN - SCOPUS:0242329380
VL - 52
SP - 693
EP - 698
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 11
ER -