A eudesmane-type sesquiterpene isolated from Pluchea odorata (L.) Cass. combats three hallmarks of cancer cells: Unrestricted proliferation, escape from apoptosis and early metastatic outgrowth in vitro

作者：Blaschke Michael; McKinnon Ruxandra; Nguyen Chi Huu; Holzner Silvio; Zehl Martin; Atanasov Atanas Georgiev; Schelch Karin; Krieger Sigurd; Diaz Rene; Frisch Richard; Feistel Bjoern; Jaeger Walter; Ecker Gerhard F; Dirsch Verena M; Grusch Michael; Zupko Istvan; Urban Ernst; Kopp Brigitte; Krupitza Georg^*

来源：Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2015, 777: 79-90.

DOI：10.1016/j.mrfmmm.2015.04.011

• Lead compound
• Anti-neoplastic
• Anti-metastatic

Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated disorders. The dichloromethane extract (DME) was tested in the carrageenan-induced rat paw oedema assay investigating its effect on inflammation that was inhibited by 37%. Also an in vitro anti-neoplastic potential was reported. However, rather limited information about the bio-activity of purified compounds and their cellular mechanisms are available. Therefore, two of the most abundant eudesmanes in P. odorata were isolated and their anti-neoplastic and anti-intravasative activities were studied. HL-60 cells were treated with P. odorata compounds and metabolic activity, cell number reduction, cell cycle progression and apoptosis induction were correlated with relevant protein expression. Tumour cell intravasation through lymph endothelial monolayers was measured and potential causal mechanisms were analyzed by Western blotting. Compound PO-1 decreased the metabolic activity of HL-60 cells (IC50=8.9 mu M after 72 h) and 10 mu M PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic activities at concentrations beyond 100 mu M. PO-1 arrested the cell cycle in G1 and this correlated with induction of JunB expression. Independent of this mechanism 25 mu M PO-1 decreased MCF-7 spheroid intravasation through the lymph endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs unrestricted proliferation and induces apoptosis at low micromolar concentrations. These results warrant further testing in vivo to challenge the potential of PO-1 as novel lead compound.

• 出版日期2015-7