Investigation of the Antiproliferative Action of the Quinoline Alkaloids Kokusaginine and Skimmianine on Human Cell Lines
Judit Molnar, Imre Ocsovszki, Laszlo Puskas, Tannaz Ghane, Judit Hohmann and István Zupko
Affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary.
Natural products play a crucial role in research into innovative antiproliferative agents. More than 60% of
anticancer drugs involve compounds of natural origin. The aim of the present study was to determine the cytotoxicity
effects of 11 quinoline alkaloids isolated from plants of the Rutaceae family. The MTT assay was used to identify the
antiproliferative effects of the tested compounds on human adherent cancer cell lines (HeLa, A431, MCF7 and A2780).
Two of these alkaloids, kokusaginine and skimmianine, were found to inhibit the proliferation of cancer cells and to
induce a cell cycle arrest in a concentration-dependent manner in HeLa cells, as evidenced by flow cytometry. A
noncancerous human fibroblast cell line (MRC-5) was used to test the selectivity of kokusaginine and skimmianine.
Fluorescent microscopy after Hoechst 33258 + propidium iodide double staining revealed concentration-dependent
nuclear condensation and disturbed cell membrane integrity. The apoptotic potentials of kokusaginine and skimmianine
were proved by assaying caspase-3. The presented results demonstrate that kokusaginine and skimmianine can be
recommended as appropriate starting structures for the design and synthesis of further quinoline analogs with improved
Keywords: Quinoline alkaloids, kokusaginine, skimmianine, cancer cells, apoptosis.
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