Antiproliferation effect of evodiamine in human colon cancer cells is associated with IGF-1/HIF-1α downregulation
| Autor: | Zhen-Hua Chen, Wen-Juan Sun, Qiu-Xiang Wu, Ying Shao, Bai-Cheng He, Yu Yu, Yu-Hua Zeng, Ke Wu, Jun Huang, Qian-Zhao Chen, Yang Li, Dong-Xu Wang, Shuang‑Xue Yuan, Chun-Mei Ren |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Colorectal cancer Pharmacology Biology Phosphatidylinositol 3-Kinases chemistry.chemical_compound Downregulation and upregulation Evodiamine Cell Line Tumor medicine Humans Insulin-Like Growth Factor I PI3K/AKT/mTOR pathway Cell Proliferation Gene knockdown Oncogene Cancer General Medicine Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Antineoplastic Agents Phytogenic Molecular medicine Gene Expression Regulation Neoplastic Oncology chemistry Colonic Neoplasms Quinazolines Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Oncology Reports. 34:3203-3211 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2015.4309 |
| Popis: | Colon cancer is one of the most common malignancies. Although the current treatment regimes for colon cancer have been well-developed in the past decades, the prognosis remains still undesirable. It is still urgent to explore new treatment strategies for colon cancer. Natural products is one of the most useful sources for anticancer agents, although some of them have serious side-effects. Evodiamine (Evo) is an quinolone alkaloid from the traditional herb medicine Evodia rutaecarpa. In the present study, we investigated the anticancer effect of Evo in human colon cancer cells. We found that Evo exhibits prominent antiproliferation and apoptosis inducing effects in LoVo cells. Evo leads to apparent downregulation of HIF-1α either in vitro or in vivo; exogenous expression of HIF-1α can attenuate the antiproliferation effect of Evo in LoVo cells, while HIF-1α knockdown potentiates this effect greatly. Further analysis indicated that Evo can also inhibit the phosphorylation of Akt1/2/3 and decrease greatly the expression of IGF-1. Thus, our findings strongly suggested that the anticancer effect of Evo in human colon cancer may be partly mediated by downregulating HIF-1α expression, which is initiated by inactivating PI3K/Akt signaling transduction though decreasing the expression of IGF-1 in colon cancer cells. Therefore, Evo may be used alone or in combination as a potential anticancer agent for colon cancer treatment. |
| Databáze: | OpenAIRE |
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