PD1-6: Antcin H isolated from antrodia cinnamomea inhibits renal cancer cell invasion through inactivation of FAK-ERK-C/EBP-B/C-FOS-MMP-7 signaling pathways and impairment of lamellipodium formation and epithelial-mesenchymal transition
  • 2017-12-22,
  • 上傳者: TUA秘書處,
  •  0
Antcin H對腎細胞癌的抑制機轉
Antcin H isolated from Antrodia cinnamomea inhibits renal cancer cell invasion through inactivation of FAK-ERK-C/EBP-b/c-Fos-MMP-7 signaling pathways and impairment of lamellipodium formation and epithelial-mesenchymal transition
Kun-Yuan Chiu1,2,3, Chiu-Yuan Chen4, Chi-Hao Chia3, Shih-Lan Hsu3,5, Yew-Min Tzeng1
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan, ROC
2 Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
3 Department of Applied Chemistry, National Chi Nan University, Puli, Nantao, Taiwan, ROC
4 Graduate Institute of Natural Healing Sciences, Nanhua University, No. 55, Section 1, Nanhua Road, Zhongkeng, Dalin Township, Chiayi County 622, Taiwan
5 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Patients with metastatic RCC show poor prognosis; therefore, novel approaches or therapeutic agents for preventing and treating progression of metastatic RCC are urgently needed. Antcin H, a natural triterpene, is purified from a famous anti-cancer medicinal mushroomAntrodia cinnamomea in Taiwan. Whether antcin H is one of the active components of Antrodia cinnamomnea with anti-cancer effect has never been explored. The aim of this study is to elucidate anti-metastatic effects and its molecular mechanisms of antcin H in human RCC 786-0 cells.
Materials and Methods:
Will be presented in the conference.
 Antcin H significantly inhibited the growth of 786-0 cells, the IC50 value (for 48 h) of antcin H was 170 mM. Besides, the migration and invasion of 786-0 cells were also drastically suppressed by antcin H under non-cytotoxic concentrations (< 100 mM), these events were accompanied by the inhibition of focal adhesion kinase (FAK) and Src kinase activities, decrease of Paxillin phosphorylation and vimentin expression, impairment of focal contact and lamellipodium formation, and up-regulation of tissue inhibitor of metalloproteinases (TIMPs) and down-regulation of several matrix metalloproteinases (MMPs), especially MMP-7 expression.
  Data from the luciferase reporter assay showed that antcin H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP-b transactivation properties. Moreover, antcin H strongly suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP-b and c-Fos on the upstream/enhancer region of MMP-7 promoter. Taken together, this is the first study to show that the anti-invasive effect of the antcin H in human renal carcinoma 786-0 cells might be at least in part by abrogating focal adhesion complex and lamellipodium formation through inhibiting the Src/FAK-paxillin signaling pathways, and decreasing MMP-7 expression through suppressing the ERK1/2-AP-1/c-Fos and C/EBP-b signaling axis.
 Our findings provide the evidence that antcin H may have the potential for application in treating metastatic RCC.
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    2017-12-22 16:28:32
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