Multidrug resistance (MDR) is a major obstacle in the treatment of cancer. MDR cells are less sensitive against structurally diverse chemotherapeutic agents, caused by the overexpression of P-glycoprotein (MDR1 or ABCB1 protein) in the cell membrane. This ATP dependent efflux protein prevents the drug molecules from reaching the effective intracellular concentration by pumping them out from the cytoplasm. Despite the great efforts, the inhibition of multidrug resistance remained an unresolved problem. Diterpenes isolated from Euphorbiaceae species represent a promising group of natural products due to their potent MDR-modulating properties.
The methanol extract of the whole plant of Euphorbia taurinensis All. was subjected to liquid-liquid partition with chloroform. Multistep chromatographic purification (CC, VLC, PLC, HPLC) yielded six pure compounds. The structure determination was carried out by means of HRMS and 1D and 2D NMR methods. The MDR modulating effects of the isolated compounds were evaluated on L5178 mouse T-lymphoma cell line using rhodamine 123 accumulation assay. The fluorescence activity ratios (FAR) between the MDR1-transfected cell populations over-expressing P-glycoprotein and its parental counterparts were measured at two concentrations (2 μM and 20 μM) by flow cytometry.
As a result of the first phytochemical investigation of E. taurinensis, two novel and four known diterpenes were obtained [1,2]. One of the new compounds possesses the rare segetane skeleton. Two diterpenes belong to the jatrophane and three compounds to the ingenane group. The occurrence of such various types of diterpenes in one species is uncommon in the genus. Four of the isolated compounds exerted substantial MDR-reversing activity on the T-lymphoma cells with FAR values between 34 and 59 at 20 μM concentration.
 Jakupovic J, Morgenstern T, Marco JA, Berendsohn W. Phytochemistry 1998; 47: 1611–1619;  Jakupovic J, Jeske F, Morgenstern T, Tsichritzis F, Marco JA, Brendsohn W. Phytochemistry 1998; 47: 1583–1600.
The research was supported by tby the European Regional Development Fund under the project GINOP-2.3.2-15-2016-00012.