Metabolomic study of natrin-induced apoptosis in SMMC-7721 hepatocellular carcinoma cells by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry

Lu, Shiyin; Lu, Rigang; Song, Hui; Wu, Jinxia; Liu, Xuwen; Zhou, Xiaoling; Yang, Jian-Qing; Zhang, Hongye; Tang, Chaoling; Guo, Hongwei; Hu, Jian; Mao, Guifu; Lin, Hanmei; Su, Zhiheng; Zheng, Heng

doi:10.1016/j.ijbiomac.2018.11.060

Cited by 10 publications

(9 citation statements)

References 51 publications

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“…Metabolomics analysis demonstrates not only individual metabolite variations, but also provides a holistic view of metabolic variations induced by biologically functional substances 22. In the present study, MetPA was used to identify the pathways involved in the anti-tumor effects of EPS1-1 on AOM/DSS-induced colorectal cancer.…”

Section: Resultsmentioning

confidence: 99%

Metabonomic Variation of Exopolysaccharide from Rhizopus nigricans on AOM/DSS-Induced Colorectal Cancer in Mice

Lü¹,

Wang²,

Ji³

et al. 2019

OTT

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BackgroundColorectal cancer (CRC), which occurs at the junction of the rectum and sigmoid colon, is a common malignancy associated with poor prognosis and high mortality worldwide. The exopolysaccharide (EPS1-1), isolated from the fermentation broth of Rhizopus nigricans (R. nigricans), has been reported to possess anti-CRC properties. However, the metabolic alterations caused by azoxymethane (AOM) and dextran sulfate sodium (DSS) are still unknown.MethodsIn the present study, a mice colon cancer model was established by treatment with AOM/DSS. LC-MS/MS-based metabolomics studies were performed to analyze metabolic alterations at the tissue level. Partial least squares discriminant analysis (PLS-DA) was used to identify differentially expressed metabolites.ResultsNineteen distinct metabolites were identified that were associated with disruptions in the following pathways: biosynthesis of unsaturated fatty acids, pyrimidine metabolism, phenylalanine metabolism, fatty acid metabolism, folate biosynthesis, and inositol phosphate metabolism. Furthermore, six significantly altered metabolites were involved in these six pathways. Compared with the Model group, the expression of cytosine, deoxyuridine, 20-hydroxy-leukotriene E4, and L-homocysteic acid was lower, whereas that of 2-dehydro-3-deoxy-6-phospho-D-gluconic acid and hematoporphyrin was higher in the EPS1-1 group.ConclusionThe results of multivariate statistical analysis demonstrate a promising application of the above metabolites by EPS1-1 in CRC therapy. Deeper understanding of the related mechanism warrants further investigation.

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Section: Resultsmentioning

confidence: 99%

Metabonomic Variation of Exopolysaccharide from Rhizopus nigricans on AOM/DSS-Induced Colorectal Cancer in Mice

Lü¹,

Wang²,

Ji³

et al. 2019

OTT

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“…However, further study is required to confirm the relation of PC and LysoPC with the apoptotic effect of PP242. Phosphatidylethanolamine (PE) is another vital element of phospholipids, and in mammalian cells, PE accounts for almost 15-25% of the total lipid content and is also associated with a vast number of physiological cellular processes [46][47][48] . In the normal cellular state, the existence of PE is only found in the inner leaflet of the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics

Rashid

Lee

Jung

2020

Sci Rep

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PP242, an inhibitor of mechanistic target of rapamycin (mTOR), displays potent anticancer effects against various cancer types. However, the underlying metabolic mechanism associated with the PP242 effects is not clearly understood. In this study, comprehensive metabolomics and lipidomics investigations were performed using ultra-high-performance chromatography-Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS) in plasma and tumor tissue to reveal the metabolic mechanism of PP242 in an LS174T cell-induced colon cancer xenograft mouse model. After 3 weeks of PP242 treatment, a reduction in tumor size and weight was observed without any critical toxicities. According to results, metabolic changes due to the effects of PP242 were not significant in plasma. In contrast, metabolic changes in tumor tissues were very significant in the PP242-treated group compared to the xenograft control (XC) group, and revealed that energy and lipid metabolism were mainly altered by PP242 treatment like other cancer inhibitors. Additionally, in this study, it was discovered that not only TCA cycle but also fatty acid β-oxidation (β-FAO) for energy metabolism was inhibited and clear reduction in glycerophospholipid was observed. This study reveals new insights into the underlying anticancer mechanism of the dual mTOR inhibitor PP242, and could help further to facilitate the understanding of PP242 effects in the clinical application.

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“…These proteins play an important role in spider toxins on ion channels and inflammation [52][53][54][55] . For example, natrin, a member of the CRISPs family isolated from the venom glands of the Chinese cobra, can inhibit lipid peroxidation and induce apoptosis of tumor cells in rat liver [56][57][58][59] . Recently, Cupiennius salei CRISP1 and CRISP2 found the C-terminal extension leading to molecular masses twice as high, which identified it in comparable cysteine-rich venom proteins from other spiders, scorpions, and from the salivary glands of ticks, so it might be arachnidspecific [60] .…”

Section: Discussionmentioning

confidence: 99%

Molecular diversity and evolutionary trends of cysteine-rich peptides from the venom glands of Chinese spider Heteropoda venatoria

Ding

Chen

Zhang

et al. 2020

Preprint

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Background: The huntsman spider ( Heteropoda venatoria Carl Linnaeus, 1767) in family Sparassidae, is highly valued in tropical and subtropical countries because the species capture and feed on cockroaches and other domestic insect pests. Unlike most other species of Araneomorphae, the huntsman spiders do not use webs to capture prey. Their great speed and strong chelicerae (mouthparts) with toxin glands are used to capture the insects.Results: We identified 154 novel putative cysteine-rich peptide toxin precursors by analyzing expressed sequence tags of the spider H. venatoria venom gland. The sequences of cysteine-rich peptide precursor revealed 24 families based on the phylogenetics analyses of signal peptide and cysteine framework in mature region, including 8 families of classic Inhibitory cystine knot toxins, 2 families of novel 6-cys motifs, 13 families of long cysteine-rich peptides with 8, 10 and 12-cys, and one family of 2-cys peptides. Intriguingly, four kinds of motifs are first described in spider venom. Furthermore, combining the diverse cysteine-rich peptide sequences of H. venatoria with the sequences from represent spiders explored previously, the dynamic evolutionary trends of venom cysteine-rich peptides were investigated based on the analysis of the structures of precursors and the patterns of cysteine scaffolds in the phylogenetic framework.Conclusion: H. venatoria is an appropriate intermediate species for the evolutionary analysis of spider peptide toxins from Mygalomorphae to Araneomorphae with a holistic view. This work revealed the dynamic evolutionary trends of venom cysteine-rich peptides of spider: the mature peptides have been developed longer with more cysteines; and the propeptides between the signal and mature peptides have been diminished and even vanished. With respect to potential insecticidal applications, the work provides promising new templates and gene clones for further exploration.

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Metabolomic study of natrin-induced apoptosis in SMMC-7721 hepatocellular carcinoma cells by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry

Cited by 10 publications

References 51 publications

<p>Metabonomic Variation of Exopolysaccharide from <em>Rhizopus nigricans</em> on AOM/DSS-Induced Colorectal Cancer in Mice</p>

<p>Metabonomic Variation of Exopolysaccharide from <em>Rhizopus nigricans</em> on AOM/DSS-Induced Colorectal Cancer in Mice</p>

Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics

Molecular diversity and evolutionary trends of cysteine-rich peptides from the venom glands of Chinese spider Heteropoda venatoria

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