Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings
| Autor: | Min-Bin Chen, Chao Ji, Mu-Xin Wei, Wen-Ting Li, Pei-Hua Lu, Mian-Hua Wu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Antineoplastic Agents Apoptosis Mice SCID mTORC1 AMP-Activated Protein Kinases colorectal cancer (CRC) Oldenlandia diffusa (OD) extracts (ODE) Oldenlandia Mice 03 medical and health sciences 0302 clinical medicine AMP-activated protein kinase Downregulation and upregulation AMP-activated protein kinase (AMPK) Cell Line Tumor Animals Humans Cytotoxic T cell Medicine Protein kinase A biology Traditional medicine Plant Extracts business.industry AMPK Middle Aged Xenograft Model Antitumor Assays p53 and mammalian target of rapamycin (mTOR) 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Signal transduction Colorectal Neoplasms business Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9969 |
| Popis: | Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings. |
| Databáze: | OpenAIRE |
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