An in vitro investigation into the anti-cancer potential of novel tetraoxane compounds for the treatment of chronic lymphocytic leukaemia /

Abstract

This study aims to evaluate the therapeutic potential of five novel tetraoxane compounds and one novel tetraoxane-naphthalimide hybrid compound for chronic lymphocytic leukaemia. These novel compounds are predicted to deliver targeted toxicity to cancer cells with reduced activity on non-cancer, healthy tissue. This selectivity is expected due to a number of properties associated with tetraoxane compounds, including the affinity of the cleavage of the endoperoxide bridge by the elevated levels of iron associated with cancer cells, and the expected production of reactive oxygen species (ROS) by cancer cells on exposure to the cytotoxic compounds. The study focuses on Chronic Lymphocytic Leukaemia, as it the most prevalent type of leukaemia in adults in the western world. However, these compounds have the potential to be equally as effective against other cancer types. The six test compounds, along with two reference compounds, Chlorambucil and Dihydroartemisinin, were evaluated on two leukaemia cell lines, HL-60 and MEC-1, and a non-cancer peripheral blood cell line, BL-2052. The anti-proliferation potential of the compounds on the leukaemia cell lines was determined and the selectivity of each compound toward the cancer cell lines over the non-cancerous BL-2052 cell line was established. Initial screening involved determination of compound IC50 values, cell membrane permeability, and analysis of mechanism of cell death, via flow cytometric analysis. The results show promising anti-cancer properties of all six compounds, with IC50 values in the low micromolar range. A comparative study of the selectivity of the compounds for leukaemic cells shows compound selectivity, with all six novel tetraoxanes less x potent against the non-cancer cell line than HL-60s. The novel compounds showed higher activity towards both leukaemic cell lines analysed in comparison to the currently utilised chemotherapeutic drug Chlorambucil. These findings show potential for these novel compounds in the endless search to provide more effective treatment options for patients while reducing adverse effects. However, further investigation of these tetraoxane compounds is required to determine their full potential