LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: The role of PKM2 in cancer progression and its structural and biological basis.

    Wu, Bingxin / Liang, Zuhui / Lan, Huan / Teng, Xiaojun / Wang, Caiyan

    Journal of physiology and biochemistry

    2024  Volume 80, Issue 2, Page(s) 261–275

    Abstract: Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase (PK), has been shown to play an important role in the development of cancer. It regulates the last step of glycolytic pathway. PKM2 has both pyruvate kinase and protein kinase activity, and the ... ...

    Abstract Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase (PK), has been shown to play an important role in the development of cancer. It regulates the last step of glycolytic pathway. PKM2 has both pyruvate kinase and protein kinase activity, and the conversion of these two functions of PKM2 depends on the mutual change of dimer and tetramer. The dimerization of PKM2 can promote the proliferation and growth of tumor cells, so inhibiting the dimerization of PKM2 is essential to curing cancer. The aggregation of PKM2 is regulated by both endogenous and exogenous cofactors as well as post-translational modification (PTM). Although there are many studies on the different aggregation of PKM2 in the process of tumor development, there are few summaries in recent years. In this review, we first introduce the role of PKM2 in various biological processes of tumor growth. Then, we summarize the aggregation regulation mechanism of PKM2 by various endogenous cofactors such as Fructose-1, 6-diphosphate (FBP), various amino acids, and post-translational modification (PTMs). Finally, the related inhibitors and agonists of PKM2 are summarized to provide reference for regulating PKM2 aggregation in the treatment of cancer in the future.
    MeSH term(s) Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/genetics ; Neoplasms/enzymology ; Thyroid Hormones/metabolism ; Carrier Proteins/metabolism ; Carrier Proteins/genetics ; Thyroid Hormone-Binding Proteins ; Protein Processing, Post-Translational ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Animals ; Disease Progression ; Cell Proliferation ; Protein Multimerization ; Pyruvate Kinase/metabolism ; Pyruvate Kinase/genetics ; Pyruvate Kinase/chemistry
    Chemical Substances Thyroid Hormones ; Carrier Proteins ; Thyroid Hormone-Binding Proteins ; Membrane Proteins ; Pyruvate Kinase (EC 2.7.1.40)
    Language English
    Publishing date 2024-02-08
    Publishing country Spain
    Document type Journal Article ; Review
    ZDB-ID 1325104-1
    ISSN 1877-8755 ; 0034-9402 ; 1138-7548
    ISSN (online) 1877-8755
    ISSN 0034-9402 ; 1138-7548
    DOI 10.1007/s13105-024-01007-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 198: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut β-GUS.

    Wang, Caiyan / Teng, Xiaojun / Wang, Chuang / Liu, Binjie / Zhou, Runze / Xu, Xueyu / Qiu, Huawei / Fu, Yu / Sun, Rongjin / Liang, Zuhui / Zhang, Rong / Liu, Zhongqiu / Zhang, Lin / Zhu, Lijun

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Volume 120, Page(s) 155040

    Abstract: Background: Irinotecan (CPT-11, Camptosar: Purpose: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, ... ...

    Abstract Background: Irinotecan (CPT-11, Camptosar
    Purpose: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for β-GUS from the gut microbiota.
    Methods: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of β-GUS in intestine were examined. We also resolved the 3D structure of β-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit β-GUS.
    Results: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of β-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of β-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT.
    Conclusions: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.
    MeSH term(s) Animals ; Mice ; Glucuronidase ; Irinotecan ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Cytokines ; Diarrhea/chemically induced ; Diarrhea/drug therapy
    Chemical Substances Glucuronidase (EC 3.2.1.31) ; Irinotecan (7673326042) ; shosaiko-to ; RNA, Ribosomal, 16S ; Cytokines
    Language English
    Publishing date 2023-08-19
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.155040
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4115: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the PI3K/AKT signaling pathway.

    Hou, Xuenan / Zhou, Chishun / Liang, Zuhui / Qiu, Huawei / Zhou, Zhuming / Zheng, Huanjin / Li, Zeyun / Wang, Ying / Qi, Xiaoxiao / Lu, Linlin / Cao, Yang / Zheng, Jing

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Volume 121, Page(s) 155093

    Abstract: Background: KRAS mutation is a common driver of NSCLC, and there is a high proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was previously considered an "undruggable" target, but the first KRAS G12C mutation-targeted drug AMG510, ...

    Abstract Background: KRAS mutation is a common driver of NSCLC, and there is a high proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was previously considered an "undruggable" target, but the first KRAS G12C mutation-targeted drug AMG510, entered the market in 2021. However, treatments for G12D mutant tumors remain to be discovered. Salvianolic acid F (SalF), a monomer derived from the traditional Chinese medicine Salvia miltiorrhiza (SM), and KRAS had high binding affinity, especially for KRAS G12D. There is an urgent need to investigate effective and safe novel targeted therapies against KRAS G12D-driven NSCLC.
    Methods: To evaluate the anticancer effect of SalF, we used KRAS-overexpressing lung cancer cells in vitro, a subcutaneous transplant tumor model, and KRAS G12D mice model in vivo. Then, the binding effect of SalF and KRAS was investigated using molecular docking, proteolytic assays and protein thermal shift assays. More critically, the PI3K/AKT signaling pathway in the lung was investigated utilizing RT-qPCR and Western Blotting.
    Results: This is the first study to evaluate the anticancer effect of SalF on KRAS-overexpressing lung cancer cells or KRAS G12D lung tumors in vivo. We demonstrated that SalF inhibits OE-KRAS A549 cell migration, proliferation and promotes apoptosis in vitro. In addition, we used a subcutaneous transplant tumor model to show that SalF suppresses the growth of lung cancer cells in vivo. Interestingly, our group found that SalF was strongly bound to G12D and could decrease the stability and promoted the degradation of the KRAS G12D mutant through molecular docking, proteolytic assays and protein thermal shift assays. Further research demonstrated that in the Kras
    Conclusion: SalF activated apoptosis signaling pathways, suppressed anti-apoptotic genes, and inhibited lung cancer cell growth. These datas suggested that SalF could effectively inhibit the growth of lung tumors with KRAS G12D mutation. SalF may be a novel inhibitor against KRAS G12D, providing a strong theoretical basis for the clinical treatment of lung cancer with KRAS mutations.
    MeSH term(s) Humans ; Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Molecular Docking Simulation ; Cell Proliferation ; Signal Transduction ; Lung Neoplasms/pathology ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Transformation, Neoplastic ; Mutation ; Cell Line, Tumor ; Lung/pathology
    Chemical Substances Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; salvianolic acid ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; KRAS protein, human
    Language English
    Publishing date 2023-09-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.155093
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4115: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top