Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
J Ethnopharmacol. 2011 Jun 1;135(3):762-71. doi: 10.1016/j.jep.2011.04.016. Epub 2011 Apr 14.
ETHNOPHARMACOLOGICAL RELAVENCE: Physalis angulata is well-known in traditional Chinese medicine as a ingredient for various herbal formulation; also, it has been shown to exhibit anti-cancer and anti-inflammatory effects. In this study, the ability of P. angulata to inhibit tumor metastasis and angiogenesis was investigated.
Anti-proliferative activity of ethyl acetate extracts of P. angulata (PA extracts), was determined against human oral squamous carcinoma (HSC-3) and human umbilical vein endothelial cells (HUVECs) by trypan blue exclusion method. Wound-healing migration, trans-well invasion, Western blotting and chick chorioallantoic membrane assay were carried out to determine the anti-metastatic and anti-angiogenic effects of PA extracts in vitro and in vivo.
We demonstrated that at sub-cytotoxic concentrations of PA extracts (5-15 μg/mL) markedly inhibited the migration and invasion of highly metastatic HSC-3 cells as shown by wound-healing repair assay and trans-well assay. Gelatin zymography assay showed that PA extracts suppressed the activity of matrix metalloproteinase (MMP)-9 and -2, and urokinase plasminogen activator (u-PA) in HSC-3 cells. In addition, Western blot analysis confirmed that PA extracts significantly decreased MMP-2 and u-PA protein expression in HSC-3 cells. Notably, PA extracts significantly augmented the expression of their endogenous inhibitors, including tissue inhibitors of MMP (TIMP-1 and -2), and plasminogen activator inhibitors (PAI-1 and -2). Further investigations revealed that non-cytotoxic concentration of PA extracts (5-15 μg/mL) inhibited vascular endothelial growth factor (VEGF)-induced proliferation, and migration/invasion of HUVECs in vitro. PA extracts also suppressed the activity of MMP-9, but not MMP-2, in HUVECs. Further, we observed, PA extracts strongly suppressed neovessel formation in the chorioallantoic membrane of chick embryos in vivo.
These results strongly support an anti-metastatic and anti-angiogenic activity of P. angulata that may contribute to the development of better chemopreventive agent for cancer and inflammation.
探讨番木瓜属植物抑制肿瘤转移和血管生成的能力。
采用台盼蓝排斥法测定番木瓜属植物乙酸乙酯提取物（PA 提取物）对人口腔鳞癌细胞（HSC-3）和人脐静脉内皮细胞（HUVEC）的增殖抑制活性。采用划痕愈合迁移、Transwell 侵袭、Western blot 及鸡胚尿囊膜试验，检测 PA 提取物在体外和体内的抗转移和抗血管生成作用。
我们发现，在亚细胞毒性浓度的 PA 提取物（5-15μg/ml）下，PA 提取物明显抑制了高度转移性 HSC-3 细胞的迁移和侵袭，如划痕愈合修复试验和 Transwell 试验所示。明胶酶谱分析显示，PA 提取物抑制了基质金属蛋白酶（MMP）-9 和 -2 以及尿激酶纤溶酶原激活物（u-PA）在 HSC-3 细胞中的活性。此外，Western blot 分析证实，PA 提取物显著降低了 HSC-3 细胞中 MMP-2 和 u-PA 蛋白的表达。值得注意的是，PA 提取物显著增加了它们内源性抑制剂的表达，包括基质金属蛋白酶抑制剂（TIMP-1 和 -2）和纤溶酶原激活物抑制剂（PAI-1 和 -2）。进一步的研究表明，非细胞毒性浓度的 PA 提取物（5-15μg/ml）抑制了血管内皮生长因子（VEGF）诱导的 HUVEC 增殖以及迁移/侵袭。PA 提取物还抑制了 MMP-9 的活性，但不抑制 MMP-2 的活性。此外，我们观察到，PA 提取物在体内强烈抑制了鸡胚尿囊膜中新血管的形成。
这些结果强烈支持番木瓜属植物具有抗转移和抗血管生成活性，这可能有助于开发更好的癌症和炎症化学预防剂。
