RT Journal Article SR Electronic T1 Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1407 OP 1414 VO 38 IS 3 A1 DONIKA IVANOVA A1 ZHIVKO ZHELEV A1 DESSISLAVA LAZAROVA A1 PLAMEN GETSOV A1 RUMIANA BAKALOVA A1 ICHIO AOKI YR 2018 UL http://ar.iiarjournals.org/content/38/3/1407.abstract AB Background/Aim: Recent studies provided convincing evidence for the anticancer activity of combined application of vitamin C and pro-vitamin K3 (menadione). The molecular pathways underlying this process are still not well established. The present study aimed to investigate the effect of the combination of vitamin C plus pro-vitamin K3 on the redox status of leukemia and normal lymphocytes, as well as their sensitizing effect for a variety of anticancer drugs. Materials and Methods: Cytotoxicity of the substances was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by fluorescein isothiocyanate-annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen and nitrogen species and protein–carbonyl products. Results: Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%, but did not influence the viability of normal lymphocytes. All combinations of anticancer drug plus vitamins C and K3 were characterized by synergistic cytotoxicity towards Jurkat cells, compared to cells treated with drug alone for 24 h. In the case of barasertib and everolimus, this synergistic cytotoxicity increased within 72 hours. It was accompanied by strong induction of apoptosis, but a reduction of level of hydroperoxides and moderately increased protein–carbonyl products in leukemia cells. Conclusion: Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes. The combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy.