Abstract | PURPOSE: We tried to clarify the cytotoxic mechanism of VK(3) using the breast cancer cell line MCF-7. METHODS: Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured. RESULTS: VK(3) exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC(50) of 14.2 microM. JC-1 staining revealed that VK(3) caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9. CONCLUSIONS: Our findings demonstrate that VK(3)-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.
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Authors | Takeshi Akiyoshi, Sumio Matzno, Mika Sakai, Noboru Okamura, Kenji Matsuyama |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 65
Issue 1
Pg. 143-50
(Dec 2009)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 19449007
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Reactive Oxygen Species
- Vitamin K 3
- Caspase 7
- Caspase 9
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Topics |
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, metabolism)
- Caspase 7
(drug effects, metabolism)
- Caspase 9
(drug effects, metabolism)
- Cell Line, Tumor
- DNA Fragmentation
(drug effects)
- Drug Screening Assays, Antitumor
- Electrophoresis, Agar Gel
- Female
- Humans
- Inhibitory Concentration 50
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects)
- Reactive Oxygen Species
(metabolism)
- Vitamin K 3
(administration & dosage, pharmacology)
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