INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2020
·Vol. 21
·期 9
·3385
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IF 4.556
Xin Meng,Jinrui Zhang,Hao Wu,Dahai Yu,Xuexun Fang
Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed inEscherichia coliprokaryote cell system, hereinafter termed Amuc_1434*), derived fromAkkermansia muciniphila, can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived fromAkkermansia muciniphilasuppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.Keywords:Amuc_1434*;colorectal cancer cells;proliferation;apoptosis;TRAIL
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Haiyan Xue,Yalin Tan,Baoyuan He,Yan Zhou,Bowei Ding,Yawen Wu,Jun Ma,JiaYi Wang,Wenmin Dong
Phlorizin (PZ), a naturally occurring flavonoid glycoside in Malus exhibits dual therapeutic potential as an antioxidant and antidiabetic agent, however its clinical translation is constrained by poor aqueous solubility (<0.1 mg/mL) and suboptimal bioavailability. To address these limitations, this study examined supramolecular complexation with β-lactoglobulin (β-LG), a whey protein carrier capable of hydrophobic nutrient transport and known for its immunomodulatory properties. Furthermore, the molecular binding mechanism, gastrointestinal stability, and synergistic effects of the PZ–β-LG complex on intestinal mucosal secretion were systematically characterized by integrating computational simulations, spectroscopic validation, and in vitro functional assays. Molecular dynamics simulations revealed that the PZ preferential bound within the calyx domain of β-LG (ΔG = −8.3 kcal/mol) through hydrophobic interactions and hydrogen bonding, as evidenced by emerging UV–Visible absorption peaks between 300 and 350 nm and intrinsic fluorescence spectroscopy. Simulated gastrointestinal digestion coupled with Liquid Chromatography–Tandem Mass Spectrometry(LC-MS/MS) peptidomics demonstrated a significant reduction in β-LG antigenicity reduction(52.1% vs. free β-LG; P < 0.01), which might be attributed to the enhanced gastrointestinal hydrolysis efficiency and the masking of immunoreactive epitopes Notably, 2 digestion-resistant peptides (VAGTWY-42 and LDAQSAPLR-89) persisted across all groups, suggesting potential allergenicity hotspots that may require further investigation. Cellular assessments using intestinal epithelium LS174T cells revealed that β-LG complexation reduced PZ associated cytotoxicity by 62% ( P < 0.05) while synergistically upregulating the expression of mucin-2 (MUC2) at both transcriptional (2.5-fold increase) and secretory levels (2.1-fold elevation vs. control). Overall, these findings indicate that hydrophobic-driven complexation PZ with β-LG not only enhances the bioavailability of polyphenol but also decreases the antigenicity of protein carrier in intestine cells.
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PubMed
高影响因子
Drug Design Development and Therapy
·
2017
·
IF 2.822
Jingrun Chen,Junjie Liu,Dongxiao Cui,Chaoqun Yan,Liqiang Meng,Liqian Sun,Shurong Ban,Rui Ge,Taigang Liang,Qingshan Li
This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(−)-cis-khellactones. The newly synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1–9.2 μM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
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