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Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis |
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| Authors: | Hseu You-Cheng Wu Chi-Rei Chang Hsueh-Wei Kumar K J Senthil Lin Ming-Kuem Chen Chih-Sheng Cho Hsin-Ju Huang Chun-Yin Huang Chih-Yang Lee Hong-Zin Hsieh Wen-Tsong Chung Jing-Gung Wang Hui-Min Yang Hsin-Ling |
| Institution: | a Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan b School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan c Department of Biomedical Science and Environmental Biology, Graduate Institute of Natural Products, Center of Excellence for Environmental Medicine, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan d Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan e School of Pharmacy, China Medical University, Taichung, Taiwan f Department of Pharmacology, China Medical University, Taichung, Taiwan g Department of Biological Science and Technology, China Medical University, Taichung, Taiwan h Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan i Institute of Nutrition, China Medical University, Taichung, Taiwan |
| Abstract: | Ethnopharmacological relavencePhysalis 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.Materials and methodsAnti-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.ResultsWe 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.ConclusionsThese 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. |
| Keywords: | Physalis angulata Metastasis HSC-3 cells Angiogenesis HUVECs |
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