Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.

ADINACO Research group Department of Pharmaceutical Botany and Ecology Faculty of Pharmacy Charles University Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

Department of Analytical Chemistry Faculty of Pharmacy Charles University Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice Studentska 573 Pardubice 532 10 Czech Republic

Department of Medical Biochemistry Faculty of Medicine in Hradec Kralove Charles University Simkova 870 Hradec Kralove 500 03 Czech Republic

Department of Medical Biophysics Faculty of Medicine in Hradec Kralove Charles University Simkova 870 Hradec Kralove 500 03 Czech Republic

Department of Organic and Bioorganic Chemistry Faculty of Pharmacy Charles University Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

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