potential of vitamin K₃ as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway

Purpose We tried to clarify the cytotoxic mechanism of VK₃ 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. Ca...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2009-12, Vol.65 (1), p.143-150
Main Authors: Akiyoshi, Takeshi, Matzno, Sumio, Sakai, Mika, Okamura, Noboru, Matsuyama, Kenji
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Cancer Research
Caspase 7 - drug effects
Caspase 7 - metabolism
Caspase 9 - drug effects
Caspase 9 - metabolism
Cell Line, Tumor
DNA Fragmentation - drug effects
Drug Screening Assays, Antitumor
Electrophoresis, Agar Gel
Female
Humans
Inhibitory Concentration 50
Medicine
Medicine & Public Health
Membrane Potential, Mitochondrial - drug effects
Mitochondria - drug effects
Oncology
Original Article
Pharmacology/Toxicology
Reactive Oxygen Species - metabolism
Vitamin K 3 - administration & dosage
Vitamin K 3 - pharmacology
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Summary:Purpose We tried to clarify the cytotoxic mechanism of VK₃ 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 VK₃ exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC₅₀ of 14.2 μM. JC-1 staining revealed that VK₃ 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 VK₃-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-009-1016-7