Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism

It is shown that vitamin K3- or vitamin C- induced apoptosis in leukemia cells by oxidative stress mechanism involving superoxide anion radical and hydrogen peroxide generation, activation of NF-κB, p53, c-Jun, protease caspase-3 activation and mitochondria depolarization leading to nuclei fragmentation. Cell death was more prominent when Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM) or 100:1 (300 μM: 3 μM), respectively.We provide for the first time in vitro evidence supporting a causative role for oxidative stress in VK3- and VC-induced apoptosis in Jurkat and K562 cells in a domino-like mechanism. Altogether these data suggest that VK3 and VC should be useful in the treatment of leukemia.Leukemia is a cancer of the bone marrow and blood. The cause of this hematological disorder is currently still unknown. Today, first-line therapy for the treatment of leukemia includes chemotherapy and radiotherapy. Unfortunately, secondary therapy-related acute lymphoblastic leukemia might emerge following chemotherapy and/or radiotherapy for primary malignancies [1]. Therefore, other therapeutic alternatives based on the reactivation of the apoptotic program should be pursued to eliminate cancer cells [2]. Accordingly, the use of vitamin K3 (VK3, also known as menadione [3]) and vitamin C (VC, also known as sodium ascorbate [4]) alone or in combination (VK3: VC [5]) is highly promising in cancer treatment. Yet, the precise pathway(s) by which VK3 and/or VC induce leukemia cell death are not well established. Moreover, given the complexity of death pathways within a cell, placing these pathways in the proper relationship to the drug trigger is challenging.During the last three decades, vitamin K3 has been known to display anti-tumor action both in vivo and in vitro in human cancer cell lines [4]. Several observations suggest that vitamin K3 might induce apoptosis -a type of cell death- [6] through different biochemical routes including severe d