Lithocholic bile acid induces apoptosis in human nephroblastoma cells: a non-selective treatment option

Trah, Julian; Oh, Jun; Pagerols-Raluy, Laia; Trochimiuk, Magdalena; Appl, Birgit; Heidelbach, Hannah S; Vincent, Deirdre; Saleem, Moin A.; Reinshagen, Konrad; Mühlig, Anne K; Boettcher, Michael

doi:10.1038/s41598-020-77436-w

Cited by 26 publications

(25 citation statements)

References 25 publications

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“…In recent years, the potential anti-tumor effect of bile acids has been gradually noticed. For example, TUDCA, UDCA and LCA have been found to have anti-tumor activity ( 24 – 26 ). Although these results showed a potentiation effect in inhibiting tumor growth, we noted that the drug concentrations used in these studies exceeded the safe concentrations we explored ( Figure S1 ).…”

Section: Discussionmentioning

confidence: 99%

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway

et al. 2022

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BackgroundHepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy.MethodsHepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR.ResultsIn this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR.ConclusionThis study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway

et al. 2022

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“…To investigate the potential mechanism of neutrophil-induced clotting, we analysed neutrophil supernatant by mass spectrometry and used it in turbidity experiments. Several mediators were observed in the neutrophil supernatant, including MPO, a marker of neutrophil activation 49 . Although cDNA was also observed in the supernatant, no histones (e.g., H3Cit) were detected.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro

Shi

Gauer

Baker

et al. 2021

Sci Rep

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Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.

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“…Both natural BAs and a large number of BADs have been proved efficient against many bacteria, parasites, fungi and to induce apoptosis in different types of cancerogenic cells. To mention some examples, it has been known for more than a decade that LCA induces apoptosis in neuroblastoma [71], breast cancer [72], prostate cancer [73] cells, although recently its selective effects on nephroblastoma and sarcoma cell-lines was questioned [74]. UDCA turned out to both favor and block apoptotic processes in different types of cells, according to the dosage and administration time.…”

Section: Functionalized Bas In Medicinementioning

confidence: 99%

Physiology and Physical Chemistry of Bile Acids

Gregorio

Cautela

Galantini

2021

IJMS

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Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical–physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bio-applications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science.

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Lithocholic bile acid induces apoptosis in human nephroblastoma cells: a non-selective treatment option

Cited by 26 publications

References 25 publications

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway

Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro

Physiology and Physical Chemistry of Bile Acids

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