TY - JOUR T1 - 2-Deoxy-D-glucose Sensitizes Cancer Cells to Barasertib and Everolimus by ROS-independent Mechanism(s) JF - Anticancer Research JO - Anticancer Res SP - 6623 LP - 6632 VL - 35 IS - 12 AU - ZHIVKO ZHELEV AU - DONIKA IVANOVA AU - ICHIO AOKI AU - TSUNEO SAGA AU - RUMIANA BAKALOVA Y1 - 2015/12/01 UR - http://ar.iiarjournals.org/content/35/12/6623.abstract N2 - The aim of the present study was to investigate: (i) the possibility of sensitizing cancer cells to anticancer drugs using the redox modulator 2-deoxy-D-glucose (2-DDG); (ii) to find such combinations with synergistic cytotoxic effect; (iii) and to clarify the role of reactive oxygen species (ROS) for induction of apoptosis and cytotoxicity through these combinations. The study covers 15 anticancer drugs – both conventional and new-generation. Four parameters were analyzed simultaneously in Jurkat leukemia cells, treated by drugs or 2-DDG (separately or in combination): cell viability, induction of apoptosis, levels of ROS, and level of protein-carbonyl products. Very well-expressed synergistic cytotoxic effects were found after 48-h treatment of Jurkat cells with 2-DDG in combination with: palbociclib, everolimus, lonafarnib, bortezomib, and barasertib. The synergistic cytotoxic effect of everolimus with 2-DDG was accompanied by very strong induction of apoptosis in cells, but a very strong reduction of ROS level. Changes in the levels of protein-carbonyl products were not detected. The synergistic cytotoxic effect of barasertib with 2-DDG was accompanied by very strong induction of apoptosis in cells, without any increase of ROS levels, but with an enhancement of protein-carbonyl products. ER -