title: Ethanol extract of baked Gardeniae Fructus exhibits in vitro and in vivo anti-metastatic and anti-angiogenic activities in malignant cancer cells: Role of suppression of the NF-κB and HIF-1α pathways.
abstract: Gardeniae Fructus (GF, Zhi Zi in China), a fruit of Gardenia jasminoides Ellis, has been used in traditional medicine to reduce inflammation and headache and to treat hepatic disorders, hypertension, and icterus. In recent studies, extract of raw or stir-baked GF was shown to have pharmacological activities for viral infection, thrombosis, hyperlipidemia, convulsion, inflammation, oxidative stress, and others. In addition, baked GF extract suppressed the proteolytic activities and altered the cellular morphology of tumor cells. However, the effects of ethanol extract of baked GF (EBGF) on the metastatic and angiogenic capacities of malignant tumor cells and its detailed mechanism of action have not been reported. In this study, we found that EBGF significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 and -13 and uPA expression via suppression of PMA-induced nuclear translocation of NF-κBp65. Metastatic potential, including migration, invasion, and colonization, was substantially reduced by EBGF with no cytotoxicity. In addition, EBGF attenuated tumor-induced angiogenesis, including microvessel sprouting, migration of endothelial cells (ECs), and tube formation of ECs, by inhibiting the release of pro-angiogenic factors from tumor cells. In C57BL/6 mice, we observed that daily administration of EBGF at 50 and 100 mg/kg suppressed metastatic colonization of B16F10 melanoma cells in the lungs. Furthermore, EBGF administration did not cause adverse effects, suggesting that EBGF is safe and may be a potential herbal medicine capable of controlling metastatic malignant cancers.
authors: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 701-300, Republic of Korea.
authors: Minju
authors: M
authors: Im
authors: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 701-300, Republic of Korea.
authors: Aeyung
authors: A
authors: Kim
authors: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 701-300, Republic of Korea.
authors: Jin Yeul
authors: JY
authors: Ma
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D032062:Gardenia / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010936:Plant Extracts / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; C498143:RELA protein, human; D051996:Transcription Factor RelA; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate