Liver Cancer Cell Line HepG2 Research Articles

New Carrageenan/2-Dimethyl Aminoethyl Methacrylate/Gelatin/ZnO Nanocomposite as a Localized Drug Delivery System with Synergistic Biomedical Applications

In recent years, the development of multifunctional hydrogels has gained significant attention due to their potential in various biomedical applications, including antimicrobial, antioxidant, and anticancer therapies. By integrating biocompatible polymers and nanoparticles, these hydrogels can achieve enhanced activity and targeted therapeutic effects. In this study, carrageenan/2-dimethyl aminoethyl methacrylate/gelatin (CAR/DEMA/Gelt) composite hydrogel was synthesized using microwave radiation specifically for its efficiency in enhancing cross-linking and promoting uniform nanoparticle dispersion within the matrix. Zinc oxide (ZnO) nanoparticles were incorporated into the hydrogel to form the (CAR/DEMA/Gelt/ZnO) nanocomposite. The hydrogels were characterized using FT-IR, FE-SEM, XRD, TGA, and EDX, confirming successful cross-linking and structural integrity. The nanocomposite hydrogel exhibited more enhanced antimicrobial activity than the composite hydrogel against Gram-positive Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis), with inhibition zones of 15 mm and 16 mm, respectively, while in case of the Gram-negative bacteria, Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), the inhibition zones were 29 mm and 19 mm, respectively. In addition to the unicellular fungi, Candida albicans (C. albicans), the inhibition zone was 19 mm. Moreover, the nanocomposite showed anti-inflammatory activity comparable to those of Indomethacin and antioxidant activity, with an impressive IC50 value of 33.3 ± 0.05 µg/mL. In vitro cytotoxicity assays revealed significant anticancer activity. Against the MCF-7 breast cancer cell line, the CAR/DEMA/Gelt/ZnO nanocomposite showed 72.5 ± 0.02% cell viability, which decreased to 30.8 ± 0.01% after loading doxorubicin (DOX). Similarly, against the HepG2 liver cancer cell line, the free nanocomposite displayed 59.9 ± 0.006% cell viability, which depleted to 29.9 ± 0.005% when DOX was uploaded. This CAR/DEMA/Gelt/ZnO nanocomposite hydrogel demonstrates strong potential as a multifunctional platform for targeted biomedical applications, particularly in cancer therapy.

Bioinformatics combined with network pharmacology and experimental validation to identify key biomarkers of hepatocellular carcinoma and corresponding compounds in Radix Astragali and Pueraria Mirifica.

The occurrence and death rates of primary hepatocellular carcinoma (HCC) are increasing, and there remains a shortage of effective oral medications with minimal side effects. We aim to identify potential biomarkers and compounds from Radix Astragali (RA) and Pueraria Mirifica (PM) to treat liver cancer and improve prognosis. Differentially expressed genes (DEGs) associated with HCC were identified by bioinformatics analysis of three datasets, GSE112791, GSE101685, and GSE45114. Using public databases to predict the bioactive components and possible targets of RA and PM. Target crossover from Gene Expression Omnibus (GEO) and public databases were used to identify potential biomarkers for HCC. Subsequently, validation and prognostic value analyses were performed using the Gene Expression Profile Interaction Analysis (GEPIA) platform. The Cytoscape software created a network of "compound targets" to pinpoint compounds linked to the biomarkers. Molecular docking techniques were utilized to validate the connection between these compounds and the identified biomarkers. Ultimately, the HepG2 liver cancer cell line was chosen to assess the inhibitory effect of Hederagenin (HDG) and to confirm the expression of ADH1B through Western blot analysis. In this study, four key biomarkers (NR1I2, ADH1B, NQO1, GHR) were identified. Molecular docking showed that these four core targets could form stable conformations with the corresponding compounds. As the drug concentration decreases, the inhibitory effect on HepG2 diminishes, and the survival rate of HepG2 cells significantly declines following the administration of 100 µmol/L HDG. Compared to the control, the expression of ADH1B protein is significantly increased in HepG2 cells treated with 100 µmol/L HDG. The study identified four key biomarkers (ADH1B, GHR, NQO1, NR1I2) that have prognostic ability for HCC. This study provides biomarkers and potential targeted monomeric medicines for treating HCC.

Environmentally benign synthesis of NiO nanoparticles: Potential catalysts for Knoevenagel condensation with promising anti-cancer and anti-diabetic activities

With rising environmental awareness, there is an increasing demand for sustainable practices, leading to the growing popularity of green synthetic methodologies that focus on simplicity and non-toxicity. The study presents an efficient eco-friendly route for synthesizing nickel oxide nanoparticles using the Punica granatum L. fruit juice extract. The synthesized nanoparticles were characterized by Ultraviolet–visible Diffuse Reflectance Spectroscopy (UV–Vis DRS), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Dynamic Light Scattering (DLS), Zeta potential and Brunauer-Emmett-Teller (BET) analyses. The nanoparticles exhibited a face-centered cubic phase, with an average crystallite size of 10 nm and a nearly spherical shape. The specific surface area of the nanoparticles was found to be 113.73 m2/g. The nanoparticles served as highly effective, heterogeneous, and sustainable catalysts for the Knoevenagel condensation reactions involving various substituted aromatic aldehydes and active methylene compounds under non-toxic and moderate conditions. The reactions proceeded smoothly with excellent product yields in short time frames with convenient work-up procedures, and easy catalyst recovery, exhibiting high Turnover Number (TON) and Turnover Frequency (TOF). The catalytic performance of the nanoparticles remained consistent over five reaction cycles. The nanoparticles showcased significant cytotoxicity against the human liver cancer cell line (HepG2), achieving a 70.28 % inhibition at a concentration of 112.5 μg/mL. Moreover, the nanoparticles exhibited notable anti-diabetic properties by inhibiting the action of alpha-amylase enzyme. An enzyme inhibition of 52.04 % was attained at a nanoparticle concentration of 500 µg/mL, thereby promoting the hypoglycemic effect. Overall, this study showcases innovative applications of NiO nanoparticles synthesized from Punica granatum L. fruit juice extract, including their use as catalysts for the Knoevenagel condensation reactions, as anti-cancer agents against HepG2 cells, and as anti-diabetic agents through alpha-amylase inhibition.

Synthesis and Characterization of TiO2 -CQDs Nanocomposites and Testing of Their Anticancer Potential

This work used a green approach to produce carbon quantum dots (CQDs). TiO2 nanoparticles (NPs) and TiO2–CQDs nanocomposites with different weight ratios of CQDs were organized through a facile sol-gel method. XRD showed that the anatase and rutile phases of TiO2 were polycrystalline with a tetragonal structure and that the CQDs exhibited a broad peak at (002) and a hexagonal structure. High resolution-transmission-electron microscopy revealed that the TiO2 NPs agglomerated in mostly spherical shapes and that the anatase and rutile phases of TiO2 had sizes of less than 15 and 25 nm, respectively. The CQDs had a relatively uniform diameter, a spherical shape with a highly crystalline structure, and a size below 2 nm. UV–visible spectroscopy revealed that the absorbance of the TiO2- CQDs nanocomposites increased with the increase in CQD ratio. The energy band gaps of the anatase and rutile phases were 3.07 and 2.7 eV, respectively, whereas that of CQDs was 3.14 eV. Meanwhile, the energy band gaps of the TiO2–CQDs nanocomposites decreased with the increase in CQDs ratio. The growth inhibition rates of the liver cancer HepG2 cell line and the normal cell line RD were measured after 24 hours of experience to the two TiO2 phases and TiO2–CQDs nanocomposites. The cytotoxicity test presented that the tested substances were extremely harmful to cells in cancer. Inhibition rates increased with the increase in CQDs ratio. The inhibition rate of growth in cancer cells, including the liver cancer HepG2 cell line and the normal cell line (RD), was measured for 24 hours after they were exposed to TiO2 (two phases) and TiO2-CQDs nanocomposites. The samples showed a slight effect on the normal line (RD) compared to HepG2 cancer. The highest inhibition rate was 12.11% for the CQD 0.7 sample.

Chemical profiling, cytotoxicity and mode of action of sea urchin Echinometra mathaei exoskeleton extract in HepG2 cancer cell line

Marine organisms contain several secondary metabolites with potent biological and pharma­cological activities. This research aimed to study the cytotoxicity and mechanism of action of methanol (MeOH) extract from the exoskeleton (shell and spines) of the sea urchin Echinometra Mathaei on human liver cancer cell line (HepG2). E. mathaei was collected from the intertidal zone of the Red Sea, Al-Ain Al-Sokhna, Egypt. HepG2 cells were treated with the MeOH extract for 24 and 48 hours to assess the cytotoxic activity and the potential molecular mechanisms. The expression levels of apoptosis-, autophagy-, and cell proliferation-related genes and/or proteins were measured. In addition, metabolomic profiling of the extract was performed by gas chromatography-mass spectrometry (GC-MS) analysis. The extract displayed cytotoxic activity on the liver cancer cells (IC50 29.47 and 14.97 µg/ml at 24 and 48 hours, respectively). It induced apoptosis, autophagy and inhibited cell proliferation of HepG2 cells. The metabolomic profiling showed that the extract is rich in fatty acids. These results demonstrated that the exoskeleton MeOH extract of E. mathaei induced apoptosis in HepG2 cells, confirming its cytotoxic effect. Therefore, a thorough investigation of its molecular target and structure is necessary to develop novel anticancer therapeutics from marine Sea urchins.

Preparation of new compounds with anticancer properties via the reaction of Kryptofix 5 with two organic acceptors

The new designed complexes via CT interaction between kryptofix 5 and two organic acceptors to introduce basic data that can be used to assessment of crown ether and tested the final complexes against cancer cells. This target was achieved by synthesis of a new CT- complexes of kryptofix 5 as a type of mixed nitrogen–oxygen crown ethers with π-acceptors as (2 hydroxy-3.5-dinitrobenzoic acid and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone). These obtained complexes were structurally characterized in both solid and liquid state via various chemical methods as elemental analysis, FT-IR, NMR, and UV–Visible spectroscopy, thermal degradation and physical properties were calculated. Finally, the CT complex was also tested for its anticancer activity against two human cancer cell lines; colon cancer CaCo2 and liver cancer cell line (hepG2). KEY WORDS: Anticancer, Kryptofix 5, HDNS, DDQ, Spectroscopy Bull. Chem. Soc. Ethiop. 2024, 38(6), 1639-1651. DOI: https://dx.doi.org/10.4314/bcse.v38i6.11

A comparative anticancer analysis of iron oxide nanoparticles of Hippophae rhamnoides and Cichorium intybus found in the Karakoram Range of Gilgit Baltistan against liver cancer targeting the RhoA gene

Objective The current research work focused on the evaluation of of H. rhamnoides and C. intybus Fe2O3 NPs against liver cancer cell line (HepG2) by performing antiproliferative assay targeting the RhoA gene and apoptotic pathway genes and proteins. Methods Fe2O3 NPs were synthesized using extracts of H. rhamnoides and C. intybus and characterized by UV–Vis spectroscopy, FTIR, SEM/EDS and XRD. MTT assay was used to study cytotoxicity against the HepG2 cells. Real-time qPCR and ELISA were used for the gene and protein analysis. Results An absorbance peak at 300 nm for H. rhamnoides and 289 nm for C. intybus nanoparticles were observed by UV–Vis analysis. The FTIR bands of H. rhamnoide Fe2O3 NPs suggested the presence of aldehydes, alcohols and polyols whereas bands of C. intybus Fe2O3 NPs suggested the presence of carboxyl groups, hydroxyl groups, alkynes and amines. The size of Fe2O3 NPs was found to be 27 ± 5nm for H. rhamnoides and 84 ± 4nm for C. intybus. The IC50 value of 41.69 µM for H. rhmnoides and 71.04 µM for C. intybus Fe2O3 NPs compared to plant extract (78.10 and 96.03 µM for H. rhamnoides and C. intybus, respectively) were found against HepG2 cells. The gene expression and protein levels of RhoA were decreased whereas those of bax, caspase 3, caspase 8 and caspase 9 were found increased. Conclusion Nanoparticles and extract of H. rhamnoides were found more effective as compared to C. intybus, which was evident by the results of cytotoxicity and analysis of studied genes and proteins.

Synthesis, Cytotoxicity, and Quantitative Structure–Activity Relationship Studies of Alkyl Triphenylphosphonium Pinostrobin Derivatives

AbstractPinostrobin, an isolated compound from Boesenbergia rotunda, has been shown to have potent anti‐proliferation and apoptosis effects in cancer stem‐like cells. However, its hydrophobic properties reduce its bioavailability. Eight new alkyl‐TPP+ pinostrobin derivatives were synthesized and assessed for their cytotoxicity against the human HepG2 liver cancer cell line using the alamarBlue assay. All derivatives exhibited moderate cytotoxicity, with the IC50 values ranging from 38.55–101.95 μM, and were more potent than pinostrobin and pinostrobin hydrazone (IC50>100 μM). Four alkyl‐TPP+ pinostrobin hydrazone amide derivatives showed more potent cytotoxicity than four alkyl‐TPP+ pinostrobin ester derivatives. QSAR analysis showed key 3D structural descriptors of TPP+‐based compounds responsible for cytotoxicity against HepG2 cells for the first time. The resultant 3D‐QSAR models using PLS and PCR methods were evaluated and found reliable in predicting the cytotoxicity of other TPP+‐based compounds.

Lupeol-3-carbamate Derivatives: Synthesis and Biological Evaluation as Potential Antitumor Agents.

In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50 = 5.39~9.43 μM) was exhibited by compound 3i against all three tumor cell lines. In addition, a salt reaction was performed on compound 3k (IC50 = 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound 3k·CH3I (IC50 = 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound 3k·CH3I through the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug.

Investigation of antibacterial and anticancer activities of copper, aluminum and nickel doped zinc sulfide nanoparticles

First time compared the different metals doped ZnS nanoparticles for antibacterial and liver cancer cell line. In this study, copper, aluminum and nickel doped ZnS NPs were synthesized via co-precipitation method. The XRD analysis was confirmed the presence of cubic crystal structure and crystallite size decreased from 6 to 3 nm with doping elements. While as SEM micro-grains were revealed slightly irregular and agglomerated morphology with the presence of dopant elements. The presence of different dopant elements such as Cu, Al and Ni in ZnS NPs was identified via EDX analysis. The FTIR results demonstrate various vibrational stretching and bending modes attached to the surface of ZnS nanomaterials. After that the well diffusion method was used to conduct in-vitro bioassays for evaluation of antibacterial and anticancer activities against E.coli and B.cereus, as well as HepG2 liver cancer cell line. Our findings unveil exceptional results with maximum inhibition zone of approximately 9 to 23 mm observed against E.coli and 12 to 27 mm against B.cereus, respectively. In addition, the significant reduction in cell viability was achieved against the HepG2 liver cancer cell line. These favorable results highlight the potential of Ni doped ZnS NPs for various biomedical applications. In future, the doped ZnS nanomaterials will be suitable for hyperthermia therapy and wound healing process.

RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade

BackgroundObesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated.MethodsIn this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo.ResultsIn hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling.ConclusionsOur study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.Graphical

Polydopamine Nanoparticle-Based Combined Chemotherapy and Photothermal Therapy for the Treatment of Liver Cancer.

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.

Synthesis, characterization, in vitro and in silico assessment of novel diclofenac derivative metal complexes

A novel hydrazone ligand was synthesized by condensing diclofenac hydrazide with salicylaldehyde. This ligand was then used to create complexes with cobalt(II), nickel(II), copper(II), gadolinium(III), lanthanum(III), and silver(I). Structural characterization of these compounds was achieved through various techniques, including nuclear magnetic resonance spectroscopy, infrared spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry, elemental analysis, thermal analysis, magnetic susceptibility measurements, electron spin resonance spectroscopy, X-ray diffraction, and conductivity measurements. The inhibitory effects of the synthesized compounds on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, critical targets for anti-inflammatory drugs, were assessed. Notably, the cobalt(II) and silver(I) complexes exhibited high selectivity for inhibiting COX-2, with selectivity indices of 118.75 and 105.00, respectively. The antitumor potential of the compounds was evaluated against MCF-7 (breast cancer) and HepG-2 (liver cancer) cell lines. The copper(II) and gadolinium(III) complexes demonstrated the highest efficacy, significantly inhibiting the growth of both cancer cell lines with half-maximal inhibitory concentration (IC50) values as low as 0.37 µM and 0.58 µM (MCF-7) and 0.35 µM and 0.67 µM (HepG-2), respectively. These complexes outperformed the original ligand in inhibiting cancer cell growth. In silico studies, using the SwissADME web tool and AutoDocke Vina, corroborated the experimental findings and provided insights into the compounds' physicochemical properties, pharmacokinetics, drug-likeness, and potential binding interactions with COX-1, COX-2, and the target proteins in the cancer cell lines.

Assessing anticancer, antidiabetic, and antioxidant capacities in green-synthesized zinc oxide nanoparticles and solvent-based plant extracts

Cancer and diabetes represent significant challenges in the field of biomedicine, with major and global impacts on public health. Acacia nilotica, commonly called 'gum arabic tree,' is recognized for its unique biomedical properties. The current study aimed to investigate the pharmacological potential of A. nilotica-based zinc-oxide nanoparticles (ZnO-NPs) in comparison to the ethanol and methanol-based extracts against cancer, diabetes, and oxidative stress. Green synthesis of ZnO-NPs was performed using barks of Acacia nilotica. Different techniques for the characterization of ZnO-NPs, including UV–Visible spectroscopy, Scanning Electron Microscopy, Fourier Transmission Infrared (FT-IR) spectroscopy, and X-ray Diffraction (XRD), were utilized. The morphological analysis of ZnO-NPs revealed that the fine NPs have mean particle sizes of 15 ± 1.5 nm. For the solvent based-extraction, leaves and barks were utilized and dissolved into ethanol and methanol for further processing. The MTT assay revealed that the optimum concentration of ZnO-NPs to inhibit the proliferation of liver cancer cell line HepG2 was 100 μg/mL where 67.0 % inhibition was observed; and both ethanol- and methanol-based extracts showed optimum inhibition at 100 μg/mL. The DPPH assay further demonstrated that 250 μg/mL of ZnO-NPs and 1000 μg/mL of both ethanol- and methanol-based extracts, as the optimum concentration for antioxidant activity (with 73.1 %, 68.9 % and 68.2 % inhibition respectively). The α-Glucosidase inhibition assay revealed that 250 μg/mL of ZnO-NPs and 10 μg/mL of both ethanol- and methanol-based extracts as the optimum concentration for antidiabetic activity (with 95 %, 93.7 % and 93.4 % inhibition respectively). The study provided interesting insights into the efficacy and reliability of ZnO-NPs for potential pharmacological application. Further research should be focused on examining specific pathways and the safety of ZnO-NPs in comparison to solvent-based extracts.

Pharmacologically important tetraaza macrocyclic Schiff base complexes of Zn(II), Cu(II) and Co(II): Synthesis, characterization, DFT studies, molecular docking and in vitro anti-bacterial and anti-cancer studies

A novel tetraaza macrocyclic Schiff base ligand and its metal complexes [Zn(II), Cu(II), and Co(II)] were successfully synthesized and characterized using various analytical techniques including FT-IR, NMR, ESI-MS, UV-Vis, PXRD, ESR, and TGA. The chemical reactivity and molecular geometry of the compounds were further elucidated through DFT calculations. The synthesized compounds were evaluated for their anti-bacterial activity against both Gram +ve and Gram -ve bacteria. Remarkably, the metal complexes exhibited enhanced anti-bacterial activity compared to the ligand. All compounds displayed moderate antibacterial activity against various strains, with complexes 4a and 4b demonstrating the highest inhibition against Gram +ve bacteria at 0.1 µM concentration. Furthermore, the cytotoxicity of these compounds against a human liver cancer cell line (HepG2) was assessed, revealing substantial anti-proliferative activity. Notably, the Zn(II) complex demonstrated an IC50 value comparable to the standard drug Doxorubicin. Importantly, the ligand and Zn(II) and Co(II) complexes exhibited minimal (< 5%) hemolysis at their IC50 values, suggesting their non-toxic nature. Molecular docking studies were conducted to investigate the binding interactions of the synthesized compounds with the active site of the topoisomerase IIβ enzyme (PDB ID: 4G0V), a crucial target for anti-bacterial and anti-cancer medications. Complex 4a displayed the strongest binding affinity (-8.2 kcal/mol) and the most favourable docked conformation, with multiple hydrogen bonds to the protein's active site. These results suggest its potential for further development as a therapeutic agent.

Synthesis and antiproliferative activity of CBD aromatic ester derivatives

This study involved the synthesis of a series of novel cannabidiol (CBD) aromatic ester derivatives, including CBD-8,12-diaromaticester derivatives (compounds 2a–2t) and CBD-8,12-diacetyl-21-aromaticester derivatives (compound 5a–5c). The antiproliferative activities of these compounds against human liver cancer cell lines HePG2 and HeP3B as well as human pancreatic cancer cell lines ASPC-1 and BXPC-3 were evaluated in vitro using the CCK-8 assay. The results indicated that compound 2f exhibited an IC50 value of 2.75 µM against HePG2, which is 5.32-fold higher than that of CBD. Additionally, compounds 2b and 5b demonstrated varying degrees of improved anticancer activity (IC50 5.95-9.21 µM) against HePG2.

Au-doped Fe3O4 nanoparticle as an effective nanocarrier for delivery of 5-fluorouracil anti-liver cancer drug

5-Fluorouracil (5-FU) is an important chemotherapy that is classified as an antimetabolite and is widely used in cancer treatment, particularly for liver cancer. Yet, administering high doses of 5-FU for liver cancer can result in a range of adverse effects. Therefore, employing a suitable delivery system for this important drug can greatly enhance its safety and effectiveness, leading to improved treatment outcomes and better quality of life for patients. Au-doped Fe3O4 nanoparticles have attracted significant interest in scientific research due to their unique physical and chemical properties. This study presents a straightforward and cost-effective method for synthesizing Au-doped Fe3O4 nanoparticles by using a natural reducing agent. The study involved a comprehensive analysis of the Au-doped Fe3O4 nanoparticles using various techniques such as FT-IR, XRD, XPS, FE-SEM, TEM, UV–Vis, EDS, VSM, and DLS. The delivery experiments indicated a loading capacity of approximately 78 %. The release profile showed slow release profile, dependent on pH. Therefore, 41 % release was detected under physiological pH 7.4, while a much faster release was observed at pH 5.7 (84 %) within 48 h. Moreover, the high crystallinity degree of approximately 84 % was attained for Au-doped Fe3O4, confirming this nanoparticle as an efficient drug delivery system. In another attempt, PDI and hydrated particle size distribution analyses on Au-doped Fe3O4 showed no significant change in size after 72 h. Therefore, it can be concluded that drug loaded Au-doped Fe3O4 is stable enough and maintained its efficacy after a long time of 3 days. Finally, an in vitro assessment of cellular cytotoxicity was performed on a liver cancer cell line (HepG2) to assess the safety and efficacy of the Au-doped Fe3O4 nanoparticles. The results from the MTT assay confirmed the potential of these nanoparticles as a promising vehicle for delivering 5-Fluorouracil.

A new lignan from Laggera crispata (Vahl) Hepper & J. R. I. Wood

A new lignan, 9′-O-angelyllariciresinol (1), and 20 known compounds (2–21) were isolated from the petroleum ether fraction of Laggera crispata (Vahl) Hepper & J. R. I. Wood. Their structures were identified by spectral analysis (NMR, IR, UV, and MS). Activity screening showed that compound 5 exhibited significant inhibitory effect on Staphylococcus aureus, while compound 2 exhibited significant inhibitory effect against liver cancer cell line HepG2.

Facile one-step synthesis of in situ WO3@Gr nanorods as an efficient material for antimicrobial and decoloration applications

This work examined the synthesis, antibacterial activity, and decolourisation of WO3@Graphene nanorods (WO3@Gr NR). WO3@Gr NR nanocomposite was in situ produced via a facile one-step hydrothermal process employing sodium tungstate dihydrate and exfoliated graphene as precursors. The resulted NR exhibited an average diameter of 13 nm, a large specific surface area of 53.3 m2 g−1, and a bimodal pore size distribution with an average pore size of 5.5 nm. The optical bandgap is extrapolated to be 2.75 eV. Graphene was shown to be responsible for the sample’s elaborate visible-light absorption, which improved adsorption and the ability to harvest visible light. WO3@Gr NR are more efficient against E. coli than S. aureus, killing up to 52% and 39% of cells, respectively, after two hours of treatment. When used in conjunction with invisible light, the NR killed E. coli and S. aureus by 78 and 62%, respectively. The bactericidal activity of photoinduced WO3@Gr NR was evaluated against P. aerugunosa, E. faecalis, E. coli, and S. aureus. The photocatalytic constant rates of organic dye methylene blue (MB) were determined to be 0.01 min−1. An IC50 (50% cell growth inhibition) value of 97 (μg ml−1) was determined for the nanocomposite against human liver cancer cell lines (HepG2). Our findings suggest that this nanorod may be utilised to degrade bacteria and organic colours in wastewater simultaneously while posing no risk to human health.

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.