title: Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential.
abstract: Vitamin K2 induces differentiation and apoptosis in a wide array of human cancer cell lines. Vitamin K2-mediated apoptosis proceeds much more slowly than the apoptosis induced by conventional anticancer agents. Thus, it is possible to analyze the underlying mechanism in detail. In this chapter, we focus on the pro-apoptotic effects of vitamin K2 on mitochondrial physiology with particular emphasis on changes in mitochondrial membrane potential (DeltaPsim). Upon treatment of ovarian cancer TYK-nu cells with vitamin K2, superoxide is produced after two to three days, followed shortly thereafter by release of mitochondrial cytochrome c. This is accompanied by other apoptotic features such as characteristic morphological changes and DNA fragmentation by day four. Data suggest that superoxide production might cause damage to mitochondrial membranes, open permeability transition pores, and result in disruption of DeltaPsim with subsequent release of cytochrome c. Both vitamin K2-induced production of superoxide and reduction of DeltaPsim are completely inhibited by alpha-tocopherol such that cell viability is retained. Thus, we propose that the loss of DeltaPsim caused by superoxide might be the major cause of apoptosis following exposure to vitamin K2. However, other pathways may be involved since cyclosporin A failed to completely inhibit vitamin K2-induced apoptosis.
authors: Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Hatanodai, Shinagawaku, Tokyo 142-8555, Japan.
authors: Toshiko
authors: T
authors: Shibayama-Imazu
authors: Toshihiro
authors: T
authors: Aiuchi
authors: Kazuyasu
authors: K
authors: Nakaya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007938:Leukemia / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D024482:Vitamin K 2 / Q000494:pharmacology*
chemical_list: D024482:Vitamin K 2