The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

Zheng, Zhi; He, Qinsi; Xu, Li‐Yan; Bai, Hua; Zhang, Zhe; Rao, Jun; Dou, Fangfang

doi:10.1515/biol-2016-0047

Cited by 10 publications

(4 citation statements)

References 11 publications

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“…Peiminine treatment elevated the levels of 45 of 57 significantly changed metabolites, including glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), increased in treated HCT-116 cells. In particular, the markedly higher levels of amino acids in treated cells than in untreated cells likely stimulated the mTOR pathway, and increased glutamine levels to stimulated mTOR activity, which validated that peiminine treatment activates PI3K/Akt/mTOR pathway, in consistence with the findings we reported in the other studies [ 36 , 49 ].…”

Section: Discussionsupporting

confidence: 89%

Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways

Zheng

Zhang

et al. 2017

Oncotarget

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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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Section: Discussionsupporting

confidence: 89%

Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways

Zheng

Zhang

et al. 2017

Oncotarget

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“…Imperialine as a promising novel anti-cancer compound against NSCLC both in vitro and in vivo approaches 52 . The natural product peiminine represses various types of cancers including colorectal, lung cancer, gastric cancer etc as reported in previous studies [58][59][60] .…”

Section: Discussionmentioning

confidence: 88%

Integrated study of HR-LC/MS and network pharmacology to identify breast cancer-related molecular targets of Fritillaria cirrhosa D. Don active constituents in combination with molecular dynamic simulation and experimental evaluation

Bhat

Mir

Alkhanani

et al. 2023

Preprint

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Fritillaria cirrhosa D. Don is a well-known medicinal plant in Kashmir Himalya. Traditionally, it has been used to treat several diseases, most notably in the treatment of various cancers particularly lung cancer. However, there is a significant gap between scientific research and its application in conventional medicine. The aim of the current work is to provide first-hand evidences both in-vitro and in silico showing that F. cirrhosa extracts exerts anti-cancer effects against breast cancer. Bulbs of F. cirrhosa was extracted with various solvents of increasing polarity. Compounds were identified by High resolution-liquid chromatography-mass spectrometry (HR-LC/MS) technique. Phytocompounds were studied for protein targets involved in pathogenesis of breast cancer using Binding 1DB (similarity index > 0.7). Later, the protein-protein interactions (PPI) network was studied using STRING programme and compound-protein interactions using Cytoscape. In addition, molecular docking was used to investigate intermolecular interactions between the compounds and the proteins software using Autodock tool. Molecular dynamics simulations studies were also used to explore the stability of the representative CDK2 + Peiminine complex. In addition, standard in-vitro biochemical assays were used to evaluate the in-vitro antiproliferative activity of active extracts of F. cirrhosa against several breast cancer cell lines. Bioactive components and potential targets in the treatment of breast cancer were validated through network pharmacology approach. HR-LC/MS detected the presence of several secondary metabolites. Afterward, molecular docking was used to verify the effective activity of the active ingredients against the prospective targets. Additionally, Peiminine showed the highest binding energy score against CDK2 (-12.99 kcal/mol). CDK2 + Peiminine was further explored for molecular dynamics simulations. During the MD simulation study at 100 nanoseconds (ns), a stable complex formation of CDK2 + Peiminine was observed. According to molecular docking results predicted, several key targets of breast cancer bind stably with the corresponding phytocompounds of F. cirrhosa. Lastly, F. cirrhosa extracts exhibited momentous anticancer activity through in vitro studies. Overall, the most important constituents were Imperialine-3-β-glucoside and Peiminine from the F. cirrhosa bulbs has effective anti-cancer efficacy by deactivating Akt1 on the PI3K-Akt signaling pathway. Therefore, these findings emphasized the momentous anti-breast cancer activity of F. cirrhosa extracts. This may open a new window and provide a theoretical foundation for further development and utilization of F. cirrhosa medicinal plant in the treatment of breast cancer.

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“…Analogously, it was discovered that the cell viability was dose-dependently decreased in colorectal carcinoma HCT-116 cells treated with peiminine (0–400 μ M for 24 h). The positive results may ascribe the elevation of the ratio of LC3B-II/LC3B-I and the upregulation of phosphorylated Unc51-like kinase 1 (p-ULK1), phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK), caspase-9, and cleaved caspase-3 levels, as well as the damping of phosphorylated mammalian target of rapamycin (p-mTOR), p-Akt, phosphorylated phosphatase, and tensin homolog (p-PTEN) activities [ 51 ]. Furthermore, peiminine (0–400 μ M for 48 h) could trigger the death of HCT-116 cells by promoting apoptosis and autophagic flux via modulating the production of metabolites, such as glucose, glutamine, oleate, and lignocerate [ 52 ].…”

Section: Pharmacologymentioning

confidence: 99%

A Systematic Review on Traditional Uses, Sources, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicity of Fritillariae Cirrhosae Bulbus

Chen

Zhong

Yao

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Fritillariae Cirrhosae Bulbus (known as chuanbeimu in Chinese, FCB) is a famous folk medicine which has been widely used to relieve cough and eliminate phlegm for thousands of years in China. The medicine originates from dried bulbs of six species of Fritillaria which are distributed in the temperate zone of the Northern Hemisphere. Increasing attention has been paid to FCB because of its excellent medicinal value such as being antitussive, expectorant, analgesic, anticancer, anti-inflammatory, and antioxidative. During the past years, a large number of research studies have been conducted to investigate the phytochemistry, pharmacology, and pharmacokinetics of FCB. A range of compounds have been isolated and identified from FCB, including alkaloids, saponins, nucleosides, organic acids, terpenoids, and sterols. Among them, alkaloids as the main active ingredient have been illustrated to exert significant therapeutic effects on many diseases such as cancer, acute lung injury, chronic obstructive pulmonary disease, asthma, Parkinson’s disease, and diabetes. Due to the excellent medical value and low toxicity, FCB has a huge market all over the world and triggers a growing enthusiasm among researchers. However, there is still a lack of systematic review. Hence, in this work, we reviewed the FCB-based articles published in Sci Finder, Web of Science, PubMed, Google Scholar, CNKI, and other databases in the recent years. The traditional uses, sources, phytochemistry, pharmacology, pharmacokinetics, and toxicity of FCB were discussed in the review, which aims to provide a reference for further development and utilization of FCB.

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The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

Cited by 10 publications

References 11 publications

Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways

Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways

Integrated study of HR-LC/MS and network pharmacology to identify breast cancer-related molecular targets of Fritillaria cirrhosa D. Don active constituents in combination with molecular dynamic simulation and experimental evaluation

A Systematic Review on Traditional Uses, Sources, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicity of Fritillariae Cirrhosae Bulbus

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