Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells
| Autor: | Wen-Yan Ren, Jia-Hui Zhu, Jin Wang, Yu-Hua Zeng, Qian-Zhao Chen, Ying Shao, Ming Huang, Bai-Cheng He, Lin-Yun Zhou, Yun-Peng Liao, Han Wang, Yang Li, Fang He, Ke Wu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research animal structures Colorectal cancer Cell Survival Bone Morphogenetic Protein 7 Apoptosis Resveratrol 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Stilbenes medicine PTEN Humans Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation biology Oncogene PTEN Phosphohydrolase Cancer General Medicine medicine.disease Flow Cytometry HCT116 Cells Antineoplastic Agents Phytogenic Cell biology Up-Regulation 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis embryonic structures Colonic Neoplasms biology.protein Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Oncology reports. 38(1) |
| ISSN: | 1791-2431 |
| Popis: | Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, we demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, we found that Res greatly upregulates BMP7 in HCT116 cells. Exogenous BMP7 enhances the anticancer effect of Res in HCT116 cells, which was almost reversed by the BMP7 specific antibody. Res does not activate the BMPs/Smads signaling, but decreases the phosphorylation of Akt1/2/3 substantially in HCT116 cells. Exogenous BMP7 enhances the inhibitory effect of Res on the phosphorylation of Akt1/2/3, while BMP7 immunodepletion reverses this effect notably. Res markedly decreases the phosphorylation of PTEN, which can be enhanced by exogenous BMP7 but partly reversed by the BMP7 antibody. Our findings suggested that Res may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating BMP7 to decrease, at least, the phosphorylation of PTEN. |
| Databáze: | OpenAIRE |
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