Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells.
Although ascorbate (Vitamin C) has been shown to inhibit cell growth and induce cell death in variety of cancer cells, results reported in other studies are inconsistent with this conclusion. It was previously reported that ascorbate induces apoptosis in human breast cancer cells. However, the molecular mechanism for this is not clear. In this study, we demonstrate that ascorbate induces cell death through the apoptosis-inducing factor (AIF) in the human breast cancer cell lines, SK-BR3 and Hs578T, but not in a normal breast cell line, Hs578. Ascorbate treatment caused the nuclear translocation of AIF, which is retained in the mitochondria in healthy cells, but caspase cleavage is not induced. Moreover, MG132, an inhibitor of AIF release from mitochondria, blocked the induction of cell death. Furthermore, cells that had been treated with human AIF-specific siRNA resisted cell death induced by ascorbate, implying that the translocation of AIF from mitochondria to the nucleus is responsible for ascorbate-mediated cell death. Therefore, these results suggest that ascorbate activates a caspase-independent and AIF-mediated cell death pathway in human breast cancer cells, SK-BR3, and Hs578T.
Hong
Seung-Woo
SW
Research Center for Women's Diseases, Division of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Korea.
Jin
Dong-Hoon
DH
Hahm
Eun-Sil
ES
Yim
Sei-Hyun
SH
Lim
Jong-Seok
JS
Kim
Keun-Il
KI
Yang
Young
Y
Lee
Soo-Suk
SS
Kang
Jae-Seung
JS
Lee
Wang-Jae
WJ
Lee
Won-Keun
WK
Lee
Myeong-Sok
MS
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007976:Leupeptins / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects