Balestrieri Ciro, Felice Francesca, Piacente Sonia, Pizza Cosimo, Montoro Paola, Oleszek Wieslaw, Visciano Vincenzo, Balestrieri Maria Luisa
Department of Biochemistry and Biophysics, Second University of Naples, via L. De Crecchio 7, 80138 Naples, Italy.
Biochem Pharmacol. 2006 May 14;71(10):1479-87. doi: 10.1016/j.bcp.2006.01.021. Epub 2006 Mar 6.
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.
丝兰酚（A、B、C）是从丝兰树皮中分离出的酚类成分，其特征在于具有由一个C15单元和一个与白藜芦醇密切相关的芪类部分组成的不寻常螺环结构。这些新型化合物因其抗氧化和抗炎特性而备受关注。然而，它们对细胞增殖、迁移以及血小板活化因子（PAF）生物合成的影响仍不清楚。PAF是一种强效的炎症介质，已知可促进血管生成以及内皮细胞和卡波西肉瘤（KS）细胞的体外迁移。我们研究的目的是确定丝兰酚和白藜芦醇对血管内皮生长因子（VEGF）诱导的KS细胞增殖、迁移和PAF生物合成的影响。结果表明，丝兰酚（25微摩尔）在抑制VEGF诱导的KS细胞增殖方面比白藜芦醇（25微摩尔）更有效。蛋白质印迹分析显示，丝兰酚降低了VEGF诱导的p38和p42/44磷酸化，从而表明可能干扰了VEGF刺激的细胞增殖的潜在机制。此外，丝兰酚完全抑制了由乙酰辅酶A：溶血PAF乙酰转移酶催化的VEGF刺激的PAF生物合成，并通过PAF依赖性非辅酶A转乙酰酶增强了其降解（为对照的250%）。此外，丝兰酚C消除了PAF诱导的细胞运动性而言，而丝兰酚A和丝兰酚B分别将细胞迁移速度从7.6微米/小时降低到6.1微米/小时和5.6微米/小时。这些结果表明，丝兰的抗炎特性可归因于白藜芦醇和丝兰酚，并为这些新型酚类化合物的抗肿瘤和抗侵袭特性提供了首个证据。
