Oncotarget

Research Papers:

Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings

Pei-Hua Lu, Min-Bin Chen, Chao Ji, Wen-Ting Li, Mu-Xin Wei and Mian-Hua Wu _

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Oncotarget. 2016; 7:45889-45900. https://doi.org/10.18632/oncotarget.9969

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Abstract

Pei-Hua Lu1,2,*, Min-Bin Chen3,*, Chao Ji4,*, Wen-Ting Li1, Mu-Xin Wei5, Mian-Hua Wu1

1Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China

2Department of Medical Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, Jiangsu, China

3Department of Medical Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, 215300, Jiangsu, China

4Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China

5Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

*These authors have contributed equally to this work

Correspondence to:

Mian-Hua Wu, email: duoduoli772@sina.com

Keywords: colorectal cancer (CRC), Oldenlandia diffusa (OD) extracts (ODE), AMP-activated protein kinase (AMPK), p53 and mammalian target of rapamycin (mTOR)

Received: April 18, 2016     Accepted: June 03, 2016     Published: June 13, 2016

ABSTRACT

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.


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