The anti-leukemic effects of vitamin K4 by modulating the JAK/STAT signaling pathway

Vitamin K4 (VK4) is a hemostasis medicine used in clinical practice. It has also been reported to possess anti-cancer properties in types of solid tumors, however, its antitumor effects in leukemia cells are unknown. We aimed to investigate the anti-leukemia role of VK4 and the involved mechanisms.

CCK-8 was used to detect the cytotoxic activity, and flow cytometry was applied to test cell cycle, apoptosis and mitochondrial membrane potential (MMP) level in human leukemia cells. Western bolting was conducted to examine the protein expression level. A xenografting leukemia model was established to explore the anti-leukemia effects triggered by VK4 in vivo.

VK4 inhibited the proliferation of human leukemia cell lines by inducing the cell cycle arrest and mitochondrial-mediated apoptosis in HL60, Jurkat and K562 cells. MMP level was also observed to be reduced under the treatment of VK4 in these three leukemia cell lines. Further studies found that VK4 inhibited the activation of JAK-STAT signaling pathway by decreasing phosphorated JAK2 and STAT3/5. The pretreatment of AG490, an inhibitor for JAK2/3 and STAT3 could significantly reverse the effect of VK4 on cell proliferation in HL60 and K562 cells. Moreover, data from HL60-xenograft model in BALB/c nude mice demonstrated that VK4 could inhibit the proliferation of HL60 in vivo in a dose-dependent manner.

VK4 exhibited a significant anti-leukemia activity by inducing cell cycle arrest and apoptosis in human leukemia cell lines through inhibiting the JAK/STAT signaling pathway. The anti-leukemia effects both in vitro and in vivo indicated that VK4 might be developed as a promising therapeutic candidate against leukemia.