title: Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro.
abstract: 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.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Hungary. molnar.judit@pharm.u-szeged.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.affiliation: AVIDIN Ltd., H-6726 Szeged, Hungary. g.szebeni@avidinbiotech.com.
authors.forename: Gábor J
authors.initials: GJ
authors.lastname: Szebeni
authors.affiliation: Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary. csuporboglar@gmail.com.
authors.forename: Boglárka
authors.initials: B
authors.lastname: Csupor-Löffler
authors.affiliation: Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary. hajdu@pharm.u-szeged.hu.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hajdú
authors.affiliation: Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, A-1090 Vienna, Austria. thomas.szekeres@meduniwien.ac.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Szekeres
authors.affiliation: Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, A-1090 Vienna, Austria. philipp.saiko@meduniwien.ac.at.
authors.forename: Philipp
authors.initials: P
authors.lastname: Saiko
authors.affiliation: Department of Biochemistry, University of Szeged, H-6720 Szeged, Hungary. ocsovszki.imre@med.u-szeged.hu.
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.affiliation: AVIDIN Ltd., H-6726 Szeged, Hungary. laszlo@avidinbiotech.com.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.affiliation: Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary. hohmann@pharm.u-szeged.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Hungary. zupko@pharm.u-szeged.hu.
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D019306:Artemisia / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D054697:Cytostatic Agents / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D031183:Onopordum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D054697:Cytostatic Agents; D010936:Plant Extracts; D012717:Sesquiterpenes; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: apoptosis; cell cycle; leukemia cells; sesquiterpenes