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

AbstractPURPOSE:
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.
AuthorsTakeshi Akiyoshi, Sumio Matzno, Mika Sakai, Noboru Okamura, Kenji Matsuyama
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 65 Issue 1 Pg. 143-50 (Dec 2009) ISSN: 1432-0843 [Electronic] Germany
PMID19449007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Vitamin K 3
  • Caspase 7
  • Caspase 9
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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