title: Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
authors.forename: Chi-Rei
authors.initials: CR
authors.lastname: Wu
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.forename: Ming-Kuem
authors.initials: MK
authors.lastname: Lin
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chen
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Cho
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
authors.forename: Wen-Tsong
authors.initials: WT
authors.lastname: Hsieh
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D032321:Physalis; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D015849:Plasminogen Inactivators / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D015849:Plasminogen Inactivators; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A; D014568:Urokinase-Type Plasminogen Activator