Effect of Alpha-tocopheryl Succinate on the Cytotoxicity of Anticancer Drugs Towards Leukemia Lymphocytes.

BACKGROUND/AIM: This study analysed the effect of α-tocopheryl succinate (α-TS) on the redox-state of leukemia and normal lymphocytes, as well as their sensitization to fifteen anticancer drugs.

MATERIALS AND METHODS

Cell viability was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by FITC-Annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen species (ROS) and protein-carbonyl products.

RESULTS

Most combinations (α-TS plus anticancer drug) exerted additive or antagonistic effects on the proliferation and viability of leukemia lymphocytes. α-TS combined with barasertib, bortezomib or lonafarnib showed a strong synergistic cytotoxic effect, which was best expressed in the case of barasestib. It was accompanied by impressive induction of apoptosis and increased production of ROS, but insignificant changes in protein-carbonyl levels. α-TS plus barasertib did not alter the viability and did not induce oxidative stress and apoptosis in normal lymphocytes.

CONCLUSION

α-TS could be a promising adjuvant in second-line anticancer therapy, particularly in acute lymphoblastic leukemia, to reduce the therapeutic doses of barasertib, bortezomib, and lonafarnib, increasing their effectiveness and minimizing their side effects.