Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves.
Flavone eupatorin is one of the constituents of Orthosiphon stamineus, a medicinal herb used in folk medicine in South East Asia for treatment of various disorders. In our study, we investigated the antiproliferative properties of a chloroform extract of the leaves of O. stamineus and of pure eupatorin. The compound was able to reduce the number of viable cancer cells to the same extent as the extract, with IC(50) values in micromolar range. Moreover, both the eupatorin standard and the extract caused cells to arrest in the G2/M phase of the cell cycle. This clearly demonstrates that eupatorin contributes significantly to the overall extract activity. Induction of mitotic catastrophe, accompanied by key molecular events defining apoptosis, is the mechanism of eupatorin-induced cell death. Importantly, eupatorin (at the doses cytotoxic to cancer cells) did not kill normal cells; it only limited migration of HUVEC endothelial cells and their ability to create tubes. The ability of eupatorin to nonspecifically inhibit many protein kinases was proven and is the probable cause of its cellular effects. In summary, eupatorin emerges as a promising agent in anticancer research.
Faculty of Science, Palacký University & Institute of Experimental Botany, Academy of Science, Olomouc, Czech Republic. iva.doleckova@centrum.cz
Iva
I
Dolečková
Lucie
L
Rárová
Jiří
J
Grúz
Magdaléna
M
Vondrusová
Miroslav
M
Strnad
Vladimír
V
Kryštof
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D031342:Orthosiphon / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D011494:Protein Kinases / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D005419:Flavonoids; D010936:Plant Extracts; C103110:eupatorin; D011494:Protein Kinases