Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome: flow cytometric detection of apoptotic cells using APO2.7 monoclonal antibody

Abstract

We have previously reported that vitamin K2 (VK2) but not VK1 has a potent apoptosis-inducing effect on freshly isolated leukemia cells from patients with various types of leukemia. By multi-color flow cytometric analysis using monoclonal antibody (mAb), APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of VK2 on minor populations of leukemic blast cells in bone marrow from patients with myelodysplastic syndrome ( /CD33++ gated cells. In addition, VK2 performed much less effectively on CD3-positive lymphoid cells. In contrast to VK2, VK1 did not show apoptosis-inducing activity. These data suggest that VK2 may be used for treatment of patients with MDS in blastic transformation.

Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells: dichotomous nature of vitamin K2 in leukemia cells

“…In addition, as previously reported in other leukemia cell lines and primary cultured leukemia cells, 3,17 treatment with 10 m of MK4 for 72 h potently induced apoptosis of HL-60-neo cells as assessed by both morphology and flow cytometric analysis using APO2.7 mAb, an antibody which specifically detects the cells undergoing apoptosis. 17,20 In contrast, this apoptosis induction by VK2 treatment was almost completely blocked in HL-60-bcl-2 cells (Figure 2a, b). Not shown is that even though the concentration of MK4 was increased to 50 m, apoptotic induction was still not evident in HL-60-bcl-2 cells.…”

“…We have already reported that detection of the percentage of APO2.7-positive cells was consistent with the results of the TUNEL method and DNA ladder formation by 2% agarose gel electrophoresis in a limiting dilution system using apoptotic cells and non-apoptosis cells. 17 …”

“…13,14 These data appear to be consistent with our in vitro observations showing that VK2 selectively induces apoptosis of blastic populations in the bone marrow cells of patients with refractory anemia of excess of blasts (RAEB), RAEB-T and AML. 17 However, VK2 therapy has also been reported to show the improvement of cytopenias in patients with refractory anemias (RA). 14,15 This might be interpreted as either the differentiation-inducing effect or the elimination of the MDS clone by VK2 treatment.…”

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells

“…It has been shown that vitamins K1, K2 and K3 could inhibit the growth of various rodent-and human-derived neoplastic cell lines in vitro, such as oral epidermal cancer, nasopharyngeal cancer, breast cancer, leukemia and hepatocellular carcinoma (HCC) cell lines (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). In marked contrast to numerous reports demonstrating in vitro antitumor effects of vitamin K, there are few reports demonstrating in vivo antitumor effects of vitamin K. Furthermore, it has not been examined so far whether vitamin K induces antitumor effects on CRC.…”

True

“…7,16 We also investigated the effects of VK2 on the MDS-KZ cell line. As shown in Figure 3, a 72 h exposure to MK5 resulted in inhibition of cell growth in a dose-dependent manner (IC 50 : 5 M).…”