Human Liver Cancer Cell Lines Research Articles

Bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer via modulating HAT1 and increasing IL-9.

Bevacizumab is a recombinant humanized monoclonal immunoglobulin (Ig) G1 antibody of VEGF, and inhibits angiogenesis and tumor growth in hepatocellular carcinoma (HCC). Ferroptosis, a new form of regulated cell death function independently of the apoptotic machinery, has been accepted as an attractive target for pharmacological intervention; the ferroptosis pathway can enhance cell immune activity of anti-PD1 immunotherapy in HCC. In this study we investigated whether and how bevacizumab regulated ferroptosis and immune activity in liver cancer. Firstly, we performed RNA-sequencing in bevacizumab-treated human liver cancer cell line HepG2 cells, and found that bevacizumab significantly altered the expression of a number of genes including VEGF, PI3K, HAT1, SLC7A11 and IL-9 in liver cancer, bevacizumab upregulated 37 ferroptosis-related drivers, and downregulated 17 ferroptosis-related suppressors in particular. We demonstrated that bevacizumab triggered ferroptosis in liver cancer cells by driving VEGF/PI3K/HAT1/SLC7A11 axis. Clinical data confirmed that the expression levels of VEGF were positively associated with those of PI3K, HAT1 and SLC7A11 in HCC tissues. Meanwhile, we found that bevacizumab enhanced immune cell activity in tumor immune-microenvironment. We identified that HAT1 up-regulated miR-143 targeting IL-9 mRNA 3'UTR in liver cancer cells; bevacizumab treatment resulted in the increase of IL-9 levels and its secretion via VEGF/PI3K/HAT1/miR-143/IL-9 axis, which led to the inhibition of tumor growth in vivo through increasing the release of IL-2 and Granzyme B from activated CD8+ T cells. We conclude that in addition to inhibiting angiogenesis, bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer. This study provides new insight into the mechanisms by which bevacizumab synergistically modulates ferroptosis and CD8+ T cell immune activity in liver cancer.

Studying the Efficacy of Copper Oxide Loaded Graphitic Carbon Nitride Nanosheets on VEGF-Induced Angiogenesis in Chick Chorioallantoic Membrane (CAM Assay) In Vivo Studies and Cytotoxicity in Human Hep3B Liver Cancer Cell Lines

Studying the Efficacy of Copper Oxide Loaded Graphitic Carbon Nitride Nanosheets on VEGF-Induced Angiogenesis in Chick Chorioallantoic Membrane (CAM Assay) In Vivo Studies and Cytotoxicity in Human Hep3B Liver Cancer Cell Lines

Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells

BackgroundCancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.Hypothesis/PurposeIn this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.Study designAn integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.MethodsWe applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.ResultsThe mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).ConclusionOur data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

Angiogenic protein profiling, phytochemical screening and in silico anti-cancer targets validation of stem, leaves, fruit, and seeds of Calotropis procera in human liver and breast cancer cell lines

The main focus of anticancer drug discovery is on developing medications that are gentle on normal cells and should have the ability to target multiple anti-cancer pathways. Liver cancer is becoming a worldwide epidemic due to the highest occurring and reoccurring rate in some countries. Calotropis procera is a xerophytic herbal plant growing wildly in Saudi Arabia. Due to its anti-angiogenic and anticancer capabilities, “C. procera “ is a viable option for developing innovative anticancer medicines. However, no study has been done previously, to discover angiogenic and anti-cancer targets which are regulated by C. procera in liver cancer. In this study, leaves, stems, flowers, and seeds of C. procera were used to prepare crude extracts and were fractionated into four solvents of diverse polarities. These bioactivity-guided solvent fractions helped to identify useful compounds with minimal side effects. The phytoconstituents present in the leaves and stem were identified by GC-MS. In silico studies were done to predict the anti-cancer targets by major bioactive constituents present in leaves and stem extracts. A human angiogenesis antibody array was performed to profile novel angiogenic targets. The results from this study showed that C. procera extracts are an ideal anti-cancer remedy with minimum toxicity to normal cells as revealed by zebrafish in vivo toxicity screening assays. The novel antiangiogenic and anticancer targets identified in this study could be explored to design medication against liver cancer.

Anti-Cancer Effect of Cephalexin Loaded on Nano chitosan Against Humane Liver Cancer

A beta-lactam antibiotic, such as cephalexin, is frequently prescribed to treat bacterial infections. In a particular investigation, cephalexin's effectiveness was assessed when it was administered ex vivo, or outside of a living organism, to the HepG2 human liver cancer cell line subsequent to its loading onto Nano chitosan. The purpose of the study was to determine how useful cephalexin would be in this situation. Positive study results showed that the drug worked well in this particular application. The ability of cephalexin to activate p53, a protein that is essential for starting the process of programmed cell death in liver cancer cells, was discovered. This shows that cephalexin, especially in combination with Nano chitosan, may be useful in the treatment of liver cancer. Overall, the study showed that cephalexin has the ability to target liver cancer cells and activate pathways that may result in their demise. Nevertheless, more investigation and clinical testing would be required to properly evaluate the safety and effectiveness of using cephalexin in this situation.

Apigenin Suppresses MED28-Mediated Cell Growth in Human Liver Cancer Cells.

Flavonoids exhibit health-promoting benefits against multiple chronic diseases, including cancer. Apigenin (4',5,7-trihydroxyflavone), one flavonoid present in fruits and vegetables, is potentially applicable to chemoprevention. Despite considerable progress in the therapeutic regimen of liver cancer, its prognosis remains poor. MED28, a Mediator subunit for transcriptional activation, is implicated in the development of several types of malignancy; however, its role in liver cancer is unknown at present. In liver cancer, the AKT/mammalian target of rapamycin (mTOR) is one major pathway involved in the oncogenic process. The aim of this study is to investigate the role of apigenin and MED28 in AKT/mTOR signaling in liver cancer. We first identified a connectivity score of 92.77 between apigenin treatment and MED28 knockdown in several cancer cell lines using CLUE, a cloud-based software platform to assess connectivity among compounds and genetic perturbagens. Higher expression of MED28 predicted a poorer survival prognosis; MED28 expression in liver cancer tissue was significantly higher than that of normal tissue, and it was positively correlated with tumor stage and grade in The Cancer Genome Atlas Liver Cancer (TCGA-LIHC) data set. Knockdown of MED28 induced cell cycle arrest and suppressed the AKT/mTOR signaling in two human liver cancer cell lines, HepG2 and Huh 7, accompanied by less lipid accumulation and lower expression and nuclear localization of sterol regulatory element binding protein 1 (SREBP1). Apigenin inhibited the expression of MED28, and the effect of apigenin mimicked that of the MED28 knockdown. On the other hand, the AKT/mTOR signaling was upregulated when MED28 was overexpressed. These data indicated that MED28 was associated with the survival prognosis and the progression of liver cancer by regulating AKT/mTOR signaling and apigenin appeared to inhibit cell growth through MED28-mediated mTOR signaling, which may be applicable as an adjuvant of chemotherapy or chemoprevention in liver cancer.

Tailoring ZnO nanoparticles for biomedical applications: Surface functionalization of ZnO nanoparticles with 2-oxo-2H-chromene-3-carboxylic acid coupled beta-cyclodextrin for enhanced antimicrobial and anticancer effect

Nanomedicine has newly emerged as a superior alternative for the treatment of numerous life-threatening illnesses. Zinc oxide nanomaterials have attracted a lot of attention in this decade because of their enormous potential in a wide range of biomedical applications. This work describes the surface functionalization of zinc oxide nanoparticles (ZnO NPs) with 2-oxo-2H-chromene-3-carboxylic acid (3-CCA) coupled beta-cyclodextrin (β-CD) to create a biocompatible system (ZnO-β-CD-3-CCA) and the evaluation of its antimicrobial and anticancer properties. Different characterization techniques, such as X-ray powder diffraction, UV–Vis spectroscopy, FTIR, transmission, and scanning electron microscopy, were used to characterize the biocompatible system. The antimicrobial properties of the synthesized ZnO NPs and the surface functionalized ZnO-β-CD-3-CCA system were evaluated using the disc diffusion method. Modification with functionalized β-CD systems increased the bacteriostatic effect of ZnO nanoparticles against various microbes. In vitro cytotoxicity of ZnO NPs and surface functionalized ZnO-β-CD-3-CCA system was evaluated against two distinct cancer cell lines: MCF-7, Hep G2, and normal rat spleen cells employing MTT assay, and the results highlight that the selective cytotoxicity of the surface functionalized ZnO-β-CD-3-CCA system against the human breast cancer (MCF-7) and human liver cancer (Hep G2) cell lines were superior to that of ZnO NPs. Also, the developed systems were less toxic to normal rat spleen cells. This work is significant because it could result in next-generation nanoparticle-based cancer treatments that are more successful.

Abstract 1456: First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy

Abstract Liver tumor, commonly called Hepatocellular carcinoma(HCC), is the most common type of primary liver malignancy. It is the fourth leading cause of cancer-related deaths. Late diagnosis, location of the tumor, tumor burden, and metastases makes liver tumor very challenging to treat by liver transplantation, surgical procedures, and other ablation techniques like cryoablation and thermal ablation. Also, the absence of a preclinical animal model makes it challenging to develop and explore the feasibility of treatment modalities. Histotripsy is a non-invasive, non-ionizing, non-thermal, image-guided focused ultrasound ablation treatment method that uses high-pressure pulses to create acoustic cavitation, a “bubble cloud,” at the target. The bubble cloud expands and collapses, which ablates the tissue into an acellular homogenate. Pigs are ideal animal models as they closely resemble human anatomy and are significant in improving the translation to human patients. This study aimed to establish the feasibility of successfully ablating liver tumors by histotripsy using an immunocompromised porcine model to generate HepG2 human liver cancer cell line tumors in the liver of the immunocompromised pigs. The orthotopic porcine model was established using RAG2/IL2RG double knockout immunocompromised pigs. HepG2 cells were injected orthotopically into the liver of immunocompromised pigs. Three weeks after the injections, CT images and necropsy indicated successful engraftment and growth of liver tumors in the pigs. The ultrasound images and post-histotripsy treatment histology images showed confirmed ablation zones in the liver. Therefore, in conclusion, our preliminary results in the study could demonstrate, for the first time, a highly robust model of human liver cancer in a large animal model. Soon, we plan to conduct more such studies and explore all the possible utilities of these immunocompromised porcine models to develop therapeutic strategies to increase the efficacy of liver tumor ablation by histotripsy. Citation Format: Tamalika Paul, Khan M. Imran, Jessica Gannon, Brie Trusiano, Kristin Eden, Hannah Ivester, Madeline Mott, Manali Powar, Michael Edwards, Christopher Byron, Sherrie Clark-Deener, Kiho Lee, Eli Vlaisavljevich, Irving Coy Allen. First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1456.

Abstract 4393: Expression levels of T-cell factor-4 variants in hepato-gastrointestinal cancer cells and tissues

Abstract Background: We previously identified 14 variants of T-cell factor (TCF)-4, a key transcriptional factor in the canonical Wnt signaling pathway, from human liver cancer cell lines (Exp Cell Res 2011). The functional analysis of the variants demonstrated that the SxxSS motif played crucial roles in high tumorigenicity, resistance to hypoxia (PLoS ONE 2012), and EMT (Liver Int 2013). These findings suggest that expression levels and patterns of TCF-4 variants tightly regulate diverse phenotypes of cancer cells. Currently, we developed a novel RT-PCR system to quantitatively evaluate TCF-4 variant expressions by using the peptide nucleic acid (PNA)-directed PCR clamping method. Aim: To assess mRNA expression levels of TCF-4 variants in hepato-gastrointestinal cancer cell lines and colon cancer tissues, focusing on TCF-4J and TCF-4K with the presence (K) or absence (J) of the SxxSS motif. Methods: Thirteen cell lines used in this study were as follows: seven liver cancer; one fetus-derived immortalized hepatocyte; one gastric cancer; two pancreatic cancer; and two colon cancer cell lines. The liver cancer cell lines HAK-1A and HAK-1B are clonally sister cell lines. Sets of three forward primers and four reverse primers were used to generate templates for quantitative PCR (qPCR), and three fluorescence (FAM and Cy5)-tagged primers were applied to detect each variant. Thirty-nine resected human cancer and non-cancerous tissue pairs were used in the IRB-certified study (No. 19192). Results: All TCF-4 variants except TCF-4M and TCF-4X were specifically and reproducibly detected and quantified. Cancer cells derived from the colon and stomach highly expressed the TCF-4 variants, showing the highest expression in TCF-4J, while cancer cells from the liver and pancreas expressed relatively lower levels. There was no remarkable difference in the expression profile of TCF-4 variants between HAK-1A and HAK-1B. In colon cancer tissues, TCF-4J was significantly more expressed than TCF-4K. Conclusion: Although the variants had been identified from liver cancer cells, they were universally expressed in cells of other organs. TCF-4J, a variant responsible for aggressive cell phenotype, was prominently found in cancer cells of the digestive tract, where the canonical Wnt signal pathway is known to be constitutively active. A similar variant profile between two liver cancer cell lines with identical clonal origin suggests that the variant pattern in the cells reflects organ-specific traits rather than dynamic phenotypic changes during cancer cell dedifferentiation. Citation Format: Hironori Koga, Yasuko Imamura, Tomoya Sudo, Hiroyuki Suzuki, Toshimitsu Tanaka, Takahiko Sakaue, Atsutaka Masuda, Hideki Iwamoto, Toru Nakamura, Hirohisa Yano, Takumi Kawaguchi. Expression levels of T-cell factor-4 variants in hepato-gastrointestinal cancer cells and tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4393.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 μg mL-1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 μg mL-1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.

Synthesis, spectroscopic and biological characterizations of platinum(IV), ruthenium(III) and iridium(III) theophylline complexes

This study used micro-analyses, (FTIR, UV-Vis) spectra, magnetic, thermogravimetric, X-ray powder diffraction (XRD) patterns, and transmittance electron microscopy (TEM) techniques to characterize three synthesized theophylline (TPH) complexes with ruthenium(III), platinum(IV), and iridium(III) metal ions. The metal ions indicated above were found to align with the TPH drug chelate as a mono-dentate ligand via the deprotonated NH group at the nitrogen atom position N7, as verified by FTIR measurements. Additionally, the complexes conductivity and magnetic susceptibility were examined. The octahedral geometry for the synthesized complexes was proposed by the current data. Except for the iridium(III) complex, which has a non-electrolytic nature due to the presence of a chlorine atom inside the chelation sphere, the molar conductivity of the complexes in DMSO solution was electrolyte in nature. Theophylline complexes with a (metal: ligand) stoichiometry of 1:2 were produced. The TPH complexes have also been tested in vitro against G(+) bacteria (Bacillus subtilis and Staphylococcus Aureus) and G(-) bacteria (Pseudomonas aeruginosa and Escherichia coli) to evaluate their antibacterial efficacy. Human breast and liver cancer cell lines were used as a test for the TPH complexes in vitro anti-cancer properties.
 KEY WORDS: Theophylline, Metal ions, Chelation, Octahedral, Spectral analysis, Nano-particles, Biological evaluation
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 725-738. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.14

Enoxacin fluoroquinolone antibacterial agent complexes with Pt(IV), Ru(III) and Ir(III) ions: Synthesis, spectroscopic, physicochemical characterizations and biological studies

The synthesis, physicochemical characterizations, and biological investigations on the chelation of the antibiotic medication enoxacin (EXN) with certain vital metal ions, such as platinum(IV), ruthenium(III), and iridium(III) are discussed in this study. These compounds structures were interpreted based on elemental analysis and spectral measurements (FTIR, 1H-NMR, UV-Vis electronic, and XRD). The findings show that there is same coordination pathway for the chelation behavior of enoxacin complexes: a monodentate manner. The Pt(IV), Ru(III), and Ir(III) complexes are coordinated through the N atom of the piperazine ring, which is an unusual mode of coordination for this class of compounds. The dissolved complexes in DMSO were found to have non-electrolyte nature based on their molar conductance measurements. The formula for these complexes is [Pt(EXN)3(H2O)2Cl] (1), [Ru(EXN)3(H2O)3] (2), and [Ir(EXN)3(H2O)3] (3). Using scanning electron microscope (SEM) analysis and X-ray powder diffraction (XRD), the nano-scale range of the Pt(IV), Ru(III), and Ir(III) complexes has been determined. Results of in vitro cytotoxicity were examined using MCF-7 cells (human breast cancer cell line) and HepG-2 cells (human hepatocellular carcinoma) that had been grown. The cytotoxic activity of the metal complexes demonstrated a cytotoxic effect against the growth of human breast and liver cancer cell lines.
 KEY WORDS: Enoxacin, Platinum(IV), Complexity, Spectral analyses, Biological assessments
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 685-699. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.11

Abstract 2308 In-vitro Combo Treatment of Human Liver Cancer Cell (Hep-G2) Line with a Cocktail that had Inhibited Human Melanoma Cell Growth

Abstract 2308 In-vitro Combo Treatment of Human Liver Cancer Cell (Hep-G2) Line with a Cocktail that had Inhibited Human Melanoma Cell Growth

Synthesis, characterization, molecular modeling studies, and biological evaluation of metal piroxicam complexes (M = Ni(II), Pt(IV), Pd(II), Ag(I)) as antibacterial and anticancer agents.

Four piroxicam metal complexes; NiL2 , PtL2 , PdL2 , and AgL were synthesized and characterized by different techniques with enhanced antibacterial and anticancer activity. Regarding in vitro antimicrobial activity, complex NiL2 displayed potent antibacterial effect against Escherichia coli and Pseudomonas aeruginosa that was 1.9-folds higher than piroxicam (minimum inhibitory concentration [MIC] = 31.85, 65.32 µM), respectively. In case of G+ve bacteria, complex PtL2 had potent activity on Staphylococcus aureus which was 2.1-folds higher than piroxicam (MIC = 43.12 µM), while activity of complex AgL against Enterococcus faecalis was threefolds higher than piroxicam (MIC = 74.57 µM. Complexes PtL2 and PdL2 exhibited higher inhibition of DNA gyrase than piroxicam (IC50 = 6.21 µM) in the range of 1.9-1.7-folds. The in vitro antiproliferative activity depicted that all investigated complexes showed better cytotoxic effect than piroxicam, specifically Pt and Pd complexes which had lower IC50 values than piroxicam on human liver cancer cell line HepG2 by 1.8 and 1.7-folds, respectively. While Pd and Ag complexes showed 2 and 1.6-folds better effect on human colon cancer cell line HT-29 compared with piroxicam. Molecular modeling studies including docking on Stranded DNA Duplex (1juu) and DNA gyrase enzyme (1kzn) that gave good insight about interaction of complexes with target molecules, calculation of electrostatic potential map and global reactivity descriptors were performed.

Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2).

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.

Production of natural flavor compounds using Bacillus subtilis-fermented soybean meal extract and their biological potential: a comprehensive in vitro study.

This study aims to investigate the production of natural flavor compounds through the utilization of Bacillus subtilis-fermented soybean meal extract and evaluate their biological potential. The experiment involved a comprehensive in vitro investigation to assess the capabilities and effects of the produced flavor compounds. The resulting flavor compounds were subjected to various in vitro tests to assess their properties, including cytotoxicity, antioxidant activity, anticancer potential, antiviral activity, and antimicrobial activity. To enhance the fermentation process, soybean meal extract was fortified with a combination of L-Lysine and L-Threonine. Gas chromatography-mass spectrometry (GC/MS) analysis was conducted on the fermented soybean meal using two strains of Bacillus subtilis, namely NRCH123 and NRCZ144. This analysis revealed the presence of various volatile compounds in all extracts, including Butylated hydroxytoluene. The fermented soybean extract with bacillus subtilis NRCZ144 (B2) fortified with a combination of 2.5% (w/w) L-Lysine and 2.5% w/w L-threonine (SLT2) exhibited a rich profile of flavor compounds, with Eucalyptol being identified as the predominant compound. The antioxidant activity of the SLT2 extract was found to be 72.04% at a concentration of 100 μg/mL, indicating significant antioxidant potential. Furthermore, when tested against the human liver cancer cell line HepG2, the extract demonstrated anticancer activity with an IC50 value of 2.26 μg/mL. The extract exhibited potent cytotoxicity, with an IC50 value of 1.02 μg/mL. Importantly, the SLT2 extract displayed strong antibacterial and antifungal activity, even at very low concentrations. The extract's antimicrobial properties indicate its potential for inhibiting the growth of bacteria and fungi.

Boswellia serrata Ekstraktının Karaciğer Kanseri (HepG2) ve Meme Kanseri (MCF7) Hücre Hatlarında Hücre Canlılığı, Apoptotik ve Nekrotik Aktivitelerinin Belirlenmesi

Cancer is a very important disease that has existed for a very long time in the history of humanity and poses a great threat to humanity today. Today, cancer remains a global health problem. The scientific world has introduced many innovative treatment approaches, but due to the complexity of cancer cells and their resistance to treatment, significant progress has been made in the fight against cancer, but a definitive cure has not yet been found. Boswellia serrata has been used in many parts of the world for a variety of ailments from ancient times to the present day, comes from the Burseraceae family and is commonly known as white gum. B. serrata is a resin tree with very small and few leaves, as it is a plant species that grows as a small tree or shrub 4-6 meters high in the desert. In this study, B.serrata resin was obtained commercially in Gaziantep province and obtained by extraction in methanol and hexane solvents. The cytotoxic activity of B. serrata resin extract was determined by MTT Assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Apoptotic/necrotic activity was determined by double staining (Hoechst 33342 and propidium iodide). Human breast cancer (MCF7) and human liver cancer (HepG2) cell lines were used in these experiments.

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs

Background and aimsDespite the increasing number of treatment options available for liver cancer, only a small proportion of patients achieve long-term clinical benefits. Herein, we aim to develop new therapeutic approaches for liver cancer. MethodsA compound screen was conducted to identify inhibitors that could synergistically induce senescence when combined with CDK4/6 inhibitor. The combination effects of CDK4/6 inhibitor and XPO1 inhibitor on cellular senescence were investigated in a panel of human liver cancer cell lines and multiple liver cancer models. A senolytic-drug screen was performed to identify drugs that selectively killed senescent liver cancer cells. ResultsThe combination of CDK4/6 inhibitor and XPO1 inhibitor synergistically induces senescence of liver cancer cells in vitro and in vivo. The XPO1 inhibitor acts by causing accumulation of RB1 in the nucleus, leading to decreased E2F signaling and promoting senescence induction by the CDK4/6 inhibitor. Through a senolytic-drug screen, CRBN-based PROTAC ARV-825 was identified as an agent that can selectively kill senescent liver cancer cells. Upregulation of CRBN was a vulnerability of senescent liver cancer cells, making them sensitive to CRBN-based PROTAC drugs. Mechanistically, we find that USP2 directly interacts with CRBN, leading to the deubiquitination and stabilization of CRBN in senescent liver cancer cells. ConclusionOur study demonstrates a striking synergy in senescence induction of liver cancer cells through the combination of CDK4/6 inhibitor and XPO1 inhibitor. These findings also shed light on the molecular processes underlying the vulnerability of senescent liver cancer cells to CRBN-based PROTAC therapy.

Exploring Cassia mimosoïdes as a promising natural source of steroids with potent anti-cancer, urease inhibition, and antimicrobial properties.

The genus Cassia is a rich source of physiologically active secondary metabolites, including a novel compound named 21-methylene-24-ethylidene lophenol, alongside 15 known compounds. These compounds were characterized using different spectroscopic techniques. They exhibited promising antimicrobial activity, particularly against bacteria causing gastrointestinal infections. Compound 1 showed strong anti-bacterial activity against H. pylori and S. aur with MIC values of 0.28 and 0.12 μg mL-1 respectively. The study investigated their impact on H. pylori, a contributor to ulcer development, by inhibiting the urease enzyme. Inhibiting urease can reduce H. pylori's pathogenic potential, evident from the fact that the compounds evaluated toward urease enzyme showed higher inhibitory activity (1.024 ± 0.43 <IC50 > 6.678±0.11 μM) compared to standard thiourea (IC50 = 18.61 ± 0.11 μM). Molecular docking studies confirmed their inhibitory action, with compound 7 notably outperforming thiourea in inhibiting urease (-6.95 kcal mol-1vs. -3.13 kcal mol-1). Additionally, these compounds showed positive effects on liver functioning, which H. pylori can impair. Compound 9 shows the best response against human HepG2 liver cancer cell lines i.e., % viability is 14.47% ± 0.69 and IC50 is 7.8 μM ± 0.21. These compounds hold potential as lead compounds for addressing gastrointestinal and liver disorders caused by H. pylori.

Investigation of Cytotoxic, Antimicrobial and Antioxidant Activity of Echium vulgare L. Seed

Echium vulgare L. is a plant belonging to the Boraginaceae family and is used in traditional medicine for the treatment of various diseases, especially known for its anti-inflammatory and antioxidant properties. The aim of this study was to determine the cytotoxic activity of different concentrations of E. vulgare L. seed extracts obtained from methanol and hexane solvents on human breast cancer (MCF7) and human liver cancer (HepG2) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antioxidant activity of the extract obtained from methanol and hexane at the same concentrations was determined according to the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity method. Antimicrobial activity was determined by disk diffusion method and bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli and Bacillus megaterium and Candida albicans microorganisms as fungi were used for the study. The highest antibacterial activity was detected against Escherichia coli (E. coli) with a zone diameter of 16±4 mm. Seed extract of E. vulgare prepared with hexane showed the most effective cytotoxic activity on HepG2 cell line with 20% cytotoxicity rate. In antioxidant activity tests, the methanol extract of E. vulgare exhibited the highest activity with 4.5% reduction. In conclusion, seed extracts of E. vulgare appear to be a potential source for both anticancer and antimicrobial therapies.