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Cytotoxic Activity of Laserpitium latifolium L. Extract and Its Daucane and Phenylpropanoid Constituents

Višnja Popović, Arne Heyerick, Silvana Petrović, Serge Van Calenbergh, Izet Karalić, Marjan Niketić and Dieter Deforce

University of Belgrade - Faculty of Pharmacy, Department of Pharmacognosy, Vojvode Stepe 450, 11221 Belgrade, Serbia

Laboratory of Pharmacognosy and Phytochemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium

Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium

Natural History Museum, Njegoševa 51, 11000 Belgrade, Serbia

Abstract: In the search for novel cytotoxic agents, sesquiterpenoids and phenylpropanoids have provided interesting lead compounds. From the chloroform extract of the underground parts of Laserpitium latifolium , the daucane sesquiterpenoids laserpitin and acetyldesoxodehydrolaserpitin, and the phenylpropanoids laserin and latifolon were isolated as the major compounds. Acetyldesoxodehydrolaserpitin is identified for the first time in the genus Laserpitium. Using a MTT and a sulforhodamine B (SRB) assay, the cytotoxic and antiproliferative activity of the extract and compounds laserpitin, acetyldesoxodehydrolaserpitin and laserin was tested in two closely related human breast adenocarcinoma cell lines, ie. the invasive MCF 7/6 and the non-invasive MCF 7/AZ. The IC 50 values of the extract were in the range of 184.72 – 397.16 μg/mL, with the most potent effect observed in the MTT test on the MCF 7/6 line. Among the tested compounds, acetyldesoxodehydrolaserpitin exerted a most potent, concentration-dependent effect (IC 50 values of 0.60 and 0.51 m M in the MCF 7/6 cell line, and 2.29 m M and 31.87 m M in the MCF 7/AZ cell line in the MTT and SRB test, respectively). The effect of laserin was more pronounced in the MTT test (IC 50 of 4.57 and 2.46 m M in the MCF 7/6 and MCF 7/AZ, respectively).

Keywords: Daucane esters ; phenylpropanoids; Laserpitium latifolium; cytotoxic activity .