Back to Search
Start Over
Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells
- Source :
- Apoptosis : an international journal on programmed cell death. 11(9)
- Publication Year :
- 2006
-
Abstract
- We reported previously that vitamin K(2) selectively induces apoptosis in human ovary cancer cells (TYK-nu cells) and pancreatic cancer cells (MIA PaCa-2 cells) through a mitochondrion-dependent pathway. In the present study, we examined the details of the mechanism of vitamin K(2)-induced apoptosis in TYK-nu cells. We found that superoxide (O(2)(*-)) was produced by TYK-nu cells between 2 and 3 days after the start of treatment with vitamin K(2), whereas it was produced within 30 min after the start of treatment with geranylgeraniol. The vitamin K(2)-induced apoptosis was inhibited by anti-oxidants, such as alpha-tocopherol, Tiron and N-acetyl-L-cysteine (NAC). Furthermore, both the production of superoxide and the induction of apoptosis by vitamin K(2) were inhibited almost completely by cycloheximide, an inhibitor of protein synthesis, suggesting that the synthesis of enzymes for the production of superoxide might be required for these processes. In parallel with the production of superoxide, the mitochondrial transmembrane potential, as measured by staining with Mitotracker Red CMXRos, dissipated during treatment of TYK-nu cells with vitamin K(2) for 3 days. The vitamin K(2)-induced depolarization of mitochondrial membranes was completely inhibited by alpha-tocopherol and, to a lesser extent, by Tiron and NAC. Since alpha-tocopherol reacts with oxygen radicals, such as superoxide, within the hydrophobic environment of the mitochondrial membrane, we postulate that vitamin K(2)-induced oxidative stress in mitochondria might damage mitochondrial membranes, with subsequent release of cytochrome c, the activation of procaspase 3 and, eventually, apoptosis.
- Subjects :
- Cancer Research
Clinical Biochemistry
alpha-Tocopherol
Pharmaceutical Science
Apoptosis
Mitochondrion
Biology
medicine.disease_cause
Membrane Potentials
chemistry.chemical_compound
Superoxides
medicine
Tumor Cells, Cultured
Humans
Cycloheximide
Inner mitochondrial membrane
Free-radical theory of aging
Pharmacology
Ovarian Neoplasms
Superoxide
Cytochrome c
Biochemistry (medical)
Vitamin K2
Vitamin K 2
Cell Biology
Molecular biology
Acetylcysteine
Mitochondria
chemistry
biology.protein
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Female
Diterpenes
Reactive Oxygen Species
Oxidative stress
Subjects
Details
- ISSN :
- 13608185
- Volume :
- 11
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Accession number :
- edsair.doi.dedup.....309ecc8e1b60ef6b129e62804cf7f4d6