Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1α via the mTOR/p70S6K/4E-BP1 and MAPK pathways.
Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: AIM OF THE STUDY: The aim of this study was to investigate the effectiveness of imperatorin as a treatment of cancer and to identify the underlying mechanisms of its anticancer activity. MATERIALS AND METHODS: HCT116, HeLa, and Hep3B cells were used in this study. Major assays were promoter-reporter gene assay, MTT, western blot analysis, immunofluorescence assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, clonogenic assay, EdU labeling and immunofluorescence, xenografted assay, and VEGF ELISA. RESULTS: CONCLUSIONS: These results show that imperatorin inhibited HIF-1α protein synthesis by downregulating the mTOR/ p70S6K/4E-BP1 and MAPK pathways. These conclusions suggest that imperatorin is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity.
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Authors | Chunliu Mi, Juan Ma, Ke Si Wang, Hong Xiang Zuo, Zhe Wang, Ming Yue Li, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Zhe Shan Quan, Xuejun Jin |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 203
Pg. 27-38
(May 05 2017)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 28341244
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Adaptor Proteins, Signal Transducing
- Angiogenesis Inhibitors
- Antineoplastic Agents, Phytogenic
- Cell Cycle Proteins
- EIF4EBP1 protein, human
- Furocoumarins
- Hypoxia-Inducible Factor 1, alpha Subunit
- Phosphoproteins
- MTOR protein, human
- Ribosomal Protein S6 Kinases, 70-kDa
- TOR Serine-Threonine Kinases
- imperatorin
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Topics |
- Adaptor Proteins, Signal Transducing
(metabolism)
- Angelica
(chemistry)
- Angiogenesis Inhibitors
(isolation & purification, pharmacology)
- Animals
- Antineoplastic Agents, Phytogenic
(isolation & purification, pharmacology)
- Cell Cycle Proteins
- Cell Proliferation
(drug effects)
- Colonic Neoplasms
(blood supply, drug therapy, pathology)
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- Furocoumarins
(isolation & purification, pharmacology)
- HCT116 Cells
- HeLa Cells
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- MAP Kinase Signaling System
(drug effects)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neovascularization, Pathologic
(drug therapy, pathology)
- Phosphoproteins
(metabolism)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- TOR Serine-Threonine Kinases
(metabolism)
- Xenograft Model Antitumor Assays
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