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Method for Novel Anti-Cancer Drug Development using Tumor Explants of Surgical Specimens
Published on: July 29, 2011
Novel anticancer alkene lactone from Persea americana
Abiodun Falodun1, Nadja Engel, Udo Kragl
1Institute of Chemistry, University of Rostock, 18059 Rostock, Germany. faloabi@uniben.edu
Context:
Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer.
Objective:
To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana.
Materials And Methods:
The MCF-7 cells were treated with different concentrations of the pure compound for 48 h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry.
Results:
One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10 µg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12 A cell was significantly stimulated by 10 µg/mL. The IC50 value for MCF-7 cells is 20.48 µg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10 µg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10 µg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1 µg/mL of 1 caused a decrease of α4-, α6-, β1- and β3-integrin expression.
Conclusions:
The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.
