The synthesis and antitumor activity of lithocholic acid and its derivatives

He, Xing; Xing, Yajing; Gu, Xiang-Zhong; Xiao, Jie-Xin; Wang, Yingying; Yi, Zhengfang; Qiu, Wen‐Wei

doi:10.1016/j.steroids.2017.06.009

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…[4]. A significant number of published papers reports various chemical transformations of the bile acids including etherification, amidation [7,8], esterification [9], replacement of hydroxyl with keto groups [10], etc. aiming to enhance their biological activities.…”

Section: Introductionmentioning

confidence: 99%

SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION OF Ni(II), Cu(II) AND Zn(II) COMPLEXES WITH DEOXYCHOLATE LIGAND

Culiţă¹

2021

FARMACIA

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Three new complexes of Ni(II), Cu(II) and Zn(II) with deoxycholate anion, of the type M(DCA) 2 • nH 2 O (M = Cu(II) n = 4, M = Ni(II) n = 3 and M = Zn(II) n = 2) have been synthesized and characterized on the basis of elemental analysis, FTIR and UV-Vis spectroscopy, thermal analysis, molar conductivity and magnetic measurements. The cytotoxicity of the synthesized complexes was tested against HT29 human colorectal cancer cells. Applied at a concentration range of 10 -200 µg/mL, sodium deoxycholate and its metal complexes have been found to decrease viability and growth of cultured HT29 cells in a time-and concentration-dependent manner in short-term and long-term experiments. The ability of the complexes to induce pathological changes, genotoxicity and apoptosis in the treated cells has also been proved. In addition, the complexes demonstrated a cytotoxic effect in HT29-OxPt (resistant to oxaliplatin) cells, allowing to conclude that they are more pronounced cytotoxic agents as compared to the sodium deoxycholate alone. RezumatTrei noi complecși ai Ni(II), Cu(II) și Zn(II) cu anionul deoxicolat, de tipul M(DCA) 2 • nH 2 O (M = Cu(II) n = 4, M = Ni(II) n = 3 și M = Zn(II) n = 2), au fost sintetizați și caracterizați pe baza analizei elementale, a spectroscopiei FTIR și UV-Vis, analizei termice, conductivității molare și a măsurătorilor magnetice. Citotoxicitatea complecșilor sintetizați a fost testată pe celule canceroase colorectale umane HT29. La concentrații de 10 -200 µg/mL, s-a observat că deoxicolatul de sodiu și complecșii săi metalici scad viabilitatea și dezvoltarea celulelor colorectale umane HT29 cultivate, într-o manieră dependentă de timp și concentrație, în experimente pe termen scurt și pe termen lung. Capacitatea complecșilor de a induce modificări patologice, genotoxicitate și apoptoză în celulele tratate a fost de asemenea dovedită. În plus, complecșii au demonstrat un efect citotoxic asupra celulelor HT29-OxPt (rezistente la oxaliplatină), permițându-ne să concluzionăm că sunt agenți citotoxici mai puternici comparativ cu deoxicolatul de sodiu.

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Section: Introductionmentioning

confidence: 99%

SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION OF Ni(II), Cu(II) AND Zn(II) COMPLEXES WITH DEOXYCHOLATE LIGAND

Culiţă¹

2021

FARMACIA

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“…[ 26 – 28 ]. Previous reports demonstrated that LCA has a very strong antitumor effect in liver cancer cells, and the cell death mechanism is apoptosis [ 29 , 30 ]. Apoptosis is a biological cell active death process, and it is an important mechanism that the multicellular organism body regulates the body development, controls cell aging, and maintains internal environment stable [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

The Apoptosis Effect on Liver Cancer Cells of Gold Nanoparticles Modified with Lithocholic Acid

et al. 2018

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Functionalized gold nanoparticles (AuNPs) have widely applied in many fields, due to their good biocompatibility, a long drug half-life, and their bioactivity is related to their size and the modified ligands on their surface. Here, we synthesized the AuNPs capped with ligands that possess polyethylene glycol (PEG) and lithocholic acid (LCA) linked by carboxyl groups (AuNP@MPA-PEG-LCA). Our cytotoxicity results indicated that AuNP@MPA-PEG-LCA have better cell selectivity; in other words, it could inhibit the growth of multiple liver cancer cells more effectively than other cancer cells and normal cells. Apoptosis plays a role in AuNP@MPA-PEG-LCA inhibition cell proliferation, which was convincingly proved by some apoptotic index experiments, such as nuclear staining, annexin V-FITC, mitochondrial membrane potential (MMP) analysis, and AO/EB staining experiments. The most potent AuNP@MPA-PEG-LCA were confirmed to efficiently induce apoptosis through a reactive oxygen species (ROS) mediating mitochondrial dysfunction. And AuNP@MPA-PEG-LCA could be more effective in promoting programmed cell death of liver cancer cells.

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“…36 However, the potential of chronic inflammation as a therapeutic target to halt the HCC progression is still obscure. Moreover, while glucocorticoids (GCs) have been shown to enhance cell proliferation and inhibit apoptosis for most mammalian cell types, 43,44 there have not been sufficient in vitro tests of GCs on cancer cells to indicate the potential benefit of GCs on carcinogenesis. Furthermore, while the use of GCs may be harmful for skin cancer, lymphoma and breast cancer, 45,46 effects of GCs on the progression of HCC have not been fully investigated by in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

<p>Hydrocortisone Suppresses Early Paraneoplastic Inflammation And Angiogenesis To Attenuate Early Hepatocellular Carcinoma Progression In Rats</p>

Liu¹,

Cui²,

Niu³

et al. 2019

OTT

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Background: Inflammation is implicated in both hepatic cirrhosis development and hepatocellular carcinogenesis, and treatment with long-acting glucocorticoid dexamethasone prevented liver carcinogenesis in mice. However, it is unclear whether glucocorticoids have anti-inflammatory effect on hepatocellular carcinoma (HCC) and if short-acting glucocorticoids (with fewer adverse effects) inhibit paraneoplastic inflammation and HCC progression. Methods: To investigate whether different types of anti-inflammatory agents attenuate HCC progression, the current study compared effects of treatments with hydrocortisone (a shortacting glucocorticoid) or aspirin on HCC progression. HCC was induced in diethylnitrosaminetreated rats which were randomly divided into 4 groups (n=8), respectively receiving orally once daily vehicle, glucuronolactone, glucuronolactone+hydrocortisone, and glucuronolactone +aspirin. Diethylnitrosamine (DEN) was given to rats in drinking water (100mg/L) to induce HCC. At weeks 12 and 16 post-induction, effects were compared on HCC nodule formation, microvessel density, and macrophage infiltration, and levels of paraneoplastic protein expression of tumor necrosis factor (TNF)-α, p38 mitogen-activated protein kinase (p38), phosphorylated p38 (p-p38), nuclear factor (NF)-κB, interleukin (IL)-10, hepatocyte growth factor (HGF), transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF). Results: Compared to the model and glucuronolactone alone groups, HCC nodule number and microvessel density in the glucuronolactone+hydrocortisone group were significantly lower at week 12. At week 12 but not week 16, significantly lower levels of macrophages, TNF-α, p-p38, NF-κB, IL-10, HGF, TGF-β1 and VEGF were observed in the paraneoplastic tissue of the glucuronolactone+hydrocortisone group when compared with the control and glucuronolactone groups. Conclusion: The results suggest that hydrocortisone treatment reduces macrophage polarization, expression of inflammatory and anti-inflammatory cytokines, and angiogenesis in paraneoplastic tissue, and attenuates early HCC progression. Although hydrocortisone did not have attenuation effect on advanced solid tumor, the current study shows the potential benefits and supports potential clinical use of hydrocortisone in attenuating early progression of HCC, which is through suppressing paraneoplastic inflammation and angiogenesis.

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The synthesis and antitumor activity of lithocholic acid and its derivatives

Cited by 23 publications

References 25 publications

SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION OF Ni(II), Cu(II) AND Zn(II) COMPLEXES WITH DEOXYCHOLATE LIGAND

SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION OF Ni(II), Cu(II) AND Zn(II) COMPLEXES WITH DEOXYCHOLATE LIGAND

The Apoptosis Effect on Liver Cancer Cells of Gold Nanoparticles Modified with Lithocholic Acid

<p>Hydrocortisone Suppresses Early Paraneoplastic Inflammation And Angiogenesis To Attenuate Early Hepatocellular Carcinoma Progression In Rats</p>

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