title: The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akiyoshi
authors.forename: Sumio
authors.initials: S
authors.lastname: Matzno
authors.forename: Mika
authors.initials: M
authors.lastname: Sakai
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuyama
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D024483:Vitamin K 3 / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D053179:Caspase 7; D053453:Caspase 9