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  • Title: Euphorbia Species-derived Diterpenes and Coumarins as Multidrug Resistance Modulators in Human Colon Carcinoma Cells.
    Author: Wiśniewski J, Wesołowska O, Środa-Pomianek K, Paprocka M, Bielawska-Pohl A, Krawczenko A, Duarte N, Ferreira MJ, Duś D, Michalak K.
    Journal: Anticancer Res; 2016 May; 36(5):2259-64. PubMed ID: 27127131.
    Abstract:
    BACKGROUND: Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells. MATERIALS AND METHODS: Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy. RESULTS: Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells. CONCLUSION: The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency.
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