Relative effects of phenolic constituents from Yucca schidigera Roezl. bark on Kaposi's sarcoma cell proliferation, migration, and PAF synthesis.
Yuccaols (A, B, C) are phenolic constituents isolated from Yucca schidigera bark characterized by unusual spirostructures made up of a C15 unit and a stilbenic portion closely related to resveratrol. These novel compounds are of particular interest for their antioxidant and anti-inflammatory properties. However, their effects on cell proliferation, migration, and platelet-activating factor (PAF) biosynthesis remain unknown. PAF, a potent mediator of inflammation, is known to promote angiogenesis and in vitro migration of endothelial cells and Kaposi's sarcoma (KS) cells. The objective of our study was to determine the effect of Yuccaols and resveratrol on the vascular endothelial growth factor (VEGF)-induced proliferation, migration, and PAF biosynthesis in KS cells. The results indicated that Yuccaols (25 microM) were more effective than resveratrol (25 microM) in inhibiting the VEGF-induced KS cell proliferation. Western blot analysis revealed that Yuccaols reduced the VEGF-induced phosphorylation of p38 and p42/44, thus indicating a possible interference with the mechanism underlying the VEGF-stimulated cell proliferation. Furthermore, Yuccaols completely inhibited the VEGF-stimulated PAF biosynthesis catalyzed by the acetyl-CoA:lyso-PAF acetyltransferase and enhanced its degradation through the PAF-dependent CoA-independent transacetylase (250% of control). In addition, Yuccaol C abrogated the PAF-induced cell motility whereas Yuccaol A and Yuccaol B reduced the cell migration from 7.6 microm/h to 6.1 microm/h and 5.6 microm/h, respectively. These results indicate that the anti-inflammatory properties attributed to Yucca schidigera can be ascribed to both resveratrol and Yuccaols and provide the first evidences of the anti-tumor and anti-invasive properties of these novel phenolic compounds.
Department of Biochemistry and Biophysics, Second University of Naples, via L. De Crecchio 7, 80138 Naples, Italy. mluisa.balestrieri@unina2.it
Ciro
C
Balestrieri
Francesca
F
Felice
Sonia
S
Piacente
Cosimo
C
Pizza
Paola
P
Montoro
Wieslaw
W
Oleszek
Vincenzo
V
Visciano
Maria Luisa
ML
Balestrieri
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D000077185:Resveratrol; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013141:Spiro Compounds / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D027623:Yucca / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D010936:Plant Extracts; D010972:Platelet Activating Factor; D013141:Spiro Compounds; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000077185:Resveratrol