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Int. J. Mol. Sci. 2016, 17(2), 83;

Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Hungary
AVIDIN Ltd., H-6726 Szeged, Hungary
Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary
Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, A-1090 Vienna, Austria
Department of Biochemistry, University of Szeged, H-6720 Szeged, Hungary
Author to whom correspondence should be addressed.
Academic Editor: Marcello Iriti
Received: 27 October 2015 / Revised: 10 December 2015 / Accepted: 29 December 2015 / Published: 17 February 2016
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)
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Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC50 values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents. View Full-Text
Keywords: sesquiterpenes; leukemia cells; cell cycle; apoptosis sesquiterpenes; leukemia cells; cell cycle; apoptosis

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Molnár, J.; Szebeni, G.J.; Csupor-Löffler, B.; Hajdú, Z.; Szekeres, T.; Saiko, P.; Ocsovszki, I.; Puskás, L.G.; Hohmann, J.; Zupkó, I. Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro. Int. J. Mol. Sci. 2016, 17, 83.

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