title: Combination of vitamin K2 plus imatinib mesylate enhances induction of apoptosis in small cell lung cancer cell lines.
abstract: Imatinib mesylate, an inhibitor of tyrosine kinases including BCR-ABL and KIT, inhibits the growth inhibition of small cell lung cancer (SCLC) cell lines in vitro. However, clinical trials of imatinib mesylate alone in patients with SCLC resulted in unsatisfactory outcomes. Vitamin K2 (menaquinone-4: VK2) induces apoptosis and differentiation in leukemia cells. We recently reported that VK2 also induces apoptosis in lung cancer cell lines. In the present study, we focused on the in vitro combined effects of imatinib mesylate plus VK2 on SCLC cell lines such as LU-139, LU-130, NCI-H69 and NCI-H128. Treatment with imatinib mesylate and VK2 for 96 h resulted in suppression of cell growth in a dose-dependent manner in all cell lines tested. The 50% inhibitory concentration (IC50) for imatinib mesylate ranged from 17-29 microM, whereas the IC50 for VK2 ranged from 16-64 microM. Combined treatment of imatinib mesylate plus VK2 resulted in pronounced inhibition of cell growth. The morphologic features of cells treated with imatinib mesylate and VK2 were typical of apoptosis. Since VK2 is a safe medicine without prominent adverse effects, treatment of patients with SCLC could derive therapeutic benefits from a combination of imatinib mesylate and VK2.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical University, Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyazawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004338:Drug Combinations; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology; D024482:Vitamin K 2 / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004338:Drug Combinations; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019089:Stem Cell Factor; D024482:Vitamin K 2; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases