Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways
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Zhi Zheng1,2,3,*, Liting Xu1,2,*, Shuofeng Zhang4,*, Wuping Li1, Fangfang Tou1,2, Qinsi He1,2, Jun Rao1,2 and Qiang Shen3
1Department of Internal Medicine 5th Division, Jiangxi Provincial Key Laboratory of Translational Medicine and Oncology, Jiangxi Cancer Hospital, Jiangxi Cancer Center, Nanchang, 330029, PR China
2School of Graduate Study, Medical College of Nanchang University, Nanchang, 330029, PR China
3Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
4Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, 100102, PR China
*These authors have contributed equally to this work
Qiang Shen, email: firstname.lastname@example.org
Jun Rao, email: email@example.com
Keywords: colorectal cancer, peiminine, natural product, metabolomics, cancer therapy
Received: March 02, 2017 Accepted: March 29, 2017 Published: April 25, 2017
Peiminine, a compound extracted from the bulbs of Fritillaria thunbergii and traditionally used as a medication in China and other Asian countries, was reported to inhibit colorectal cancer cell proliferation and tumor growth by inducing autophagic cell death. However, its mechanism of anticancer action is not well understood, especially at the metabolic level, which was thought to primarily account for peiminine’s efficacy against cancer. Using an established metabolomic profiling platform combining ultra-performance liquid chromatography/tandem mass spectrometry with gas chromatography/mass spectrometry, we identified metabolic alterations in colorectal cancer cell line HCT-116 after peiminine treatment. Among the identified 236 metabolites, the levels of 57 of them were significantly (p < 0.05) different between peiminine-treated and -untreated cells in which 45 metabolites were increased and the other 12 metabolites were decreased. Several of the affected metabolites, including glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), may be involved in regulation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway and in the oxidative stress response upon peiminine exposure. Peiminine predominantly modulated the pathways responsible for metabolism of amino acids, carbohydrates, and lipids. Collectively, these results provide new insights into the mechanisms by which peiminine modulates metabolic pathways to inhibit colorectal cancer cell growth, supporting further exploration of peiminine as a potential new strategy for treating colorectal cancer.
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