The aim of the present study was: (i) to investigate the possibility of sensitizing
leukemia lymphocytes to anticancer drugs using
docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on
leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of
reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed
after treatment of
leukemia lymphocytes (Jurkat) with DHA in combination with:
barasertib,
lonafarnib,
everolimus, and
palbociclib. We selected two synergistic combinations, DHA with
everolimus or
barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (
leukemia and normal). At the selected concentrations, DHA,
everolimus and
barasertib (applied separately) were cytotoxic towards
leukemia lymphocytes, but not normal lymphocytes. In
leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as
everolimus and
barasertib, that is
cancer cell-specific (particularly for
acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer
chemotherapy, allowing therapeutic doses of
everolimus and
barasertib to be reduced, minimizing their side-effects.