Examination of apoptosis-inducing activity in leukemia cells by vitamin K2 and the clinical application of vitamin K2

• Project/Area Number: 10670968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo Medical University
• Principal Investigator: YAGUCHI Makoto Tokyo Medical University, Department of Medicine, Assistant, 医学部, 助手 (50246310)
• Co-Investigator(Kenkyū-buntansha): MIYAZAWA Keisuke Tokyo Medical University, Department of Medicine, Assistant Professor, 医学部, 講師 (50209897)
• Project Period (FY): 1998 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: Vitamin K2 / Leukemia / Myelodysplastic Syndrome / Apoptosis / Vitamin K2 / MDS / Apoptosis

Research Abstract

VK2 selectively induced apoptosis in leukemia cells and MDS blasts and apoptosis of VK2 was enhanced with VP16.
VK2 induced the increase of p27ィイD1KIP1ィエD1 and G1 arrest. Moreover, the differentiation antigens of the leukemia cells were increased by VK2.
VK2 treatment decreased the potential of mitochondria membrane with time and decreased the expression of BCL-2, while increased BAX. These data show VK2 acts mitochondria.
Apoptosis of VK2 was controlled by the cell growth factor such as G-CSF. The cross talk of both signals is assumed.
Moreover, we judged that the anti-cancer medicine treatment was clinical impossible to the MDS patient who was accompanied by the marrow fibrosis, and we admitted VK2 to him with his agreement. The decrease of blasts and the improvement of platelet decrease were shown after the oral administration of VK2.
The questionnaire research of the VK2 treatment to the MDS patients was done to many hospitals. We obtained the effective rate of 30% or more. Multi hospitals rule effect is scheduled based on this result for the future.

Research Products

• [Publications] Yaguchi Makoto et al: "Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome : flow cytometric detection of apoptosis cells using APO2.7 monoclonal antibody"Leukemia. 12. 1392-1397 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yaguchi Makoto et al: "Vitamin K2 therapy for a patient with myelodysplastic syndrome"Leukemia. 13. 144-145 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishimaki Jiroh et al: "Vitamin K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation"Leukemia. 13. 1399-1405 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yaguchi,M., Miyazawa,K., Otawa,M., Katagiri,T., Nishimaki,J., Uchida,Y., Iwase,O., Gotoh,A., Kawanishi,Y., Toyama,K.: "Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome : flow cytometric detection of apoptotic cells using APO2.7monoclonal antibody."Leukemia. 12(9). 1392-1397 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yaguchi,M., Miyazawa,K., Otawa,M. Ito,Y., Kawanishi,Y., Toyama,K.: "Vitamin K2 therapy for a patient with myelodysplastic syndrome."Leukemia. 13(1). 144-145 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishimaki,J., Miyazawa,K., Yaguchi,M., Katagiri,T., Kawanishi,Y., Toyama,K., Ohyashiki,K., Hashimoto,S., Nakaya,K., Takiguchi,T.,: "Vitamin K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation."Leukemia. 13(9). 1399-1405 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yaguchi Makoto et al: "Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome : Flow cytometric detection of apoptosis cells using APO2.7 monoclonal antibody"Leukemia. 12(9). 1392-1397 (1998)
• [Publications] Yaguchi Makoto et al: "Vitamin K2 therapy for a patient with myelodysplastic syndrome"Leukemia. 13(1). 144-145 (1999)
• [Publications] Nishimaki Jiroh et al: "Vitamin K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation"Leukemia. 13(9). 1399-1405 (1999)
• [Publications] Yaguchi Makoto et al: "Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome:Flow cytometric detection of apoptosis cells using APO2.7 monoclonal antibody" Leukemia. 12. 1392-1397 (1998)
• [Publications] Yaguchi Makoto et al: "Vitamin K2 therapy for a patient with myelodysplastic syndrome" Leukemia. 13. 144-145 (1999)