Effects of Vitamin K2 in Patients with Myelodysplastic Syndromes-From The Standing Point of Apoptosis Inducing Effects of Vitamin K2 on Leukemia Cells-

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We have originally reported that vitamin K2 (VK2) induces apoptosis in primary cultured leukemia cells and leukemia cell lines. This apoptosis process was mediated through down-modulation of BCL-2 repression, up-modulation of BAX, depolarization of mitochondrial membrane potential, and activation of caspase-3. Enforced over expression of BCL-2 in H-60 cell (HL-60bcl-2) resulted in almost complete inhibition of apoptosis induction in response to VK2. However, monocytic differentiation via G0/G1 arrest was still observed in HL-60bcl-2 cells. This strongly suggests that VK2. Furthermore, we have reported that this monocytic differtntionan induction is synergistically enhanced by combined treatment with VK2 and vitamin D3 analog. Interestingly, apoptosis induction in response to VK2 was significantly suppressed along with enhanced moncytitc differentiation. In response to our in vitro observations, pilot studies of VK2 therapy in-patients with myelodysplastic syndromes (MDS) and post-MDS AML were performed in many institutions in Japan. These clinical trials demonstrate the therapeutic effects of VK2 for the patients with MDS. Further moleculer-based studies are still on going to explain the mechanisms of therapeutic effects of VK2 in MDS.