Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania.

ABSTRACT: Previous work from our group showed that tamoxifen, an oral drug that has been in use for the treatment of breast cancer for over 40 years, is active both in vitro and in vivo against several species of Leishmania, the etiological agent of leishmaniasis. Using a combination of metabolic labeling with [³H]-sphingosine and myo-[³H]-inositol, alkaline hydrolysis, HPTLC fractionations and mass spectrometry analyses, we observed a perturbation in the metabolism of inositolphosphorylceramides (IPCs) and phosphatidylinositols (PIs) after treatment of L. amazonensis promastigotes with tamoxifen, with a significant reduction in the biosynthesis of the major IPCs (composed of d16:1/18:0-IPC, t16:0/C18:0-IPC, d18:1/18:0-IPC and t16:0/20:0-IPC) and PIs (sn-1-O-(C_18:0)a

SUBMITTER: Trinconi CT 

PROVIDER: S-EPMC6216108 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature