Human Liver Cancer Cells HepG2 Research Articles

Hypoxia-activated prodrug combining site-specific chemotherapy and light-driven photothermal therapy

The development of a highly effective and low toxic drug is very beneficial for precise cancer therapy. Herein, taking advantage of the hypoxic nature of tumors, we carefully designed and synthesized the first hypoxia-activated single-molecule prodrug BDP-CPT-NO2 for fluorescence imaging-guided chemo-photothermal dual-mode therapy. The prodrug contains the chemotherapeutic drug camptothecin (CPT) and a boron dipyrromethene (BDP)-based photothermal agent, which are connected through a nitroreductase (NTR)-responsive linker (a nitro unit), and shows no fluorescence and extremely low cytotoxicity under normoxia. However, the nitro in the prodrug could be reduced to amino by exogenous NTR with nicotinamide adenine dinucleotide (NADH) in PBS buffer solution and endogenous NTR in hypoxic cancer cells, which is followed by a self-immolative reaction that leads to the release of CPT and BDP-COOH. This process is accompanied by significantly enhanced BDP and CPT fluorescence, which are due to NTR-induced ester-to-carboxylate conversion and fluorescence resonance energy transfer (FRET) interruption, respectively. Concomitantly, BDP-CPT-NO2 displays powerful combined chemo-PTT therapeutic efficacy, as evidenced in human cervical cancer HeLa and human liver cancer HepG2 cells, as well as in mice bearing H22 tumors. This study provides a promising strategy for effective and selective cancer treatment by hypoxia-activated prodrugs caged within organic photothermal agents.

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.

Facile engineering of aptamer-coupled silk fibroin encapsulated myogenic gold nanocomposites: investigation of antiproliferative activity and apoptosis induction.

Nanocomposites selectively induce cancer cell death, holding potential for precise liver cancer treatment breakthroughs. This study assessed the cytotoxicity of gold nanocomposites (Au NCs) enclosed within silk fibroin (SF), aptamer (Ap), and the myogenic Talaromyces purpureogenus (TP) against a human liver cancer cell (HepG2). The ultimate product, Ap-SF-TP@Au NCs, results from a three-step process. This process involves the myogenic synthesis of TP@Au NCs derived from TP mycelial extract, encapsulation of SF on TP@Au NCs (SF-TP@Au NCs), and the conjugation of Ap within SF-TP@Au NCs. The synthesized NCs are analyzed by various characteristic techniques. Ap-SF-TP@Au NCs induced potential cell death in HepG2 cells but exhibited no cytotoxicity in non-cancerous cells (NIH3T3). The morphological changes in cells were examined through various biochemical staining methods. Thus, Ap-SF-TP@Au NCs emerge as a promising nanocomposite for treating diverse cancer cells.

Pleonotoquinones, Cytotoxic Oxepinenaphthoquinones from Pleonotoma jasminifolia.

Two unusual naphthoquinones, named here as pleonotoquinones A (1) and B (2), were isolated along with two known anthraquinones (3 and 4) via chromatographic separations of an ethyl acetate extract of the roots of Pleonotoma jasminifolia. Compounds 1 and 2 are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data. The isolated compounds were evaluated for their antiproliferative activity against human cancer cell lines, and compounds 1 and 2 displayed cytotoxicity against human colon cancer HCT116 cells (IC50 = 2.6 μM for compound 1 and IC50 = 4.3 μM for compound 2) and human liver cancer HepG2 cells (IC50 = 1.9 μM for compound 1 and IC50 = 6.4 μM for compound 2).

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.

Cryoablation with KCl Solution Enhances Necrosis and Apoptosis of HepG2 Liver Cancer Cells.

Cryoablation has become a valuable treatment modality for the management of liver cancer. However, one of the major challenges in cryosurgery is the incomplete cryodestruction near the edge of the iceball. This issue can be addressed by optimizing cryoablation parameters and administering thermotropic drugs prior to the procedure. These drugs help enhance tumor response, thereby strengthening the destruction of the incomplete frozen zone in liver cance. In the present study, the feasibility and effectiveness of a thermophysical agent, KCl solution, were investigated to enhance the cryodestruction of HepG2 human liver cancer cells. All cryoablation parameters were simultaneously optimized in order to significantly improve the effect of cryoablation, resulting in an increase in the lethal temperature from - 25°C to - 17°C. Subsequently, it was found that the application of KCl solution prior to freezing significantly decreased cell viability post-thaw compared to cryoablation treatment alone. This effect was attributed to the eutectic effect of KCl solution. Importantly, it was found that the combination of KCl solution and freezing was less effective when applied to LO2 human liver normal cells. The data revealed that the ratio of mRNA levels of Bcl-2 and bax decreased significantly more in HepG2 cells than in LO2 cells when cryoablation was used with KCl solution. In conclusion, the results of this study demonstrate the effectiveness of KCl solution in promoting cryoablation and describe a novel therapeutic model for the treatment of liver cancer that may distinguish between cancer and normal cells.

Recovery of Cembratrien-Diols from Waste Tobacco (Nicotiana tabacum L.) Flowers by Microwave-Assisted Deep Eutectic Solvent Extraction: Optimization, Separation, and In Vitro Bioactivity.

Deep eutectic solvents (DESs) are novel solvents with physicochemical properties similar to those of ionic liquids, and they have attracted extensive attention for the extraction of bioactive compounds from different plant materials in the context of green chemistry and sustainable development. In this study, seven DESs with different polarities were explored as green extraction solvents for cembratrien-diols (CBT-diols) from waste tobacco flowers. The best solvent, DES-3 (choline chloride: lactic acid (1:3)), which outperformed conventional solvents (methanol, ethanol, and ethyl acetate), was selected and further optimized for microwave-assisted DES extraction using the response surface methodology. The maximum yield of CBT-diols (6.23 ± 0.15 mg/g) was achieved using a microwave power of 425 W, microwave time of 32 min, solid/liquid ratio of 20 mg/mL, and microwave temperature of 40 °C. Additionally, the isolated CBT-diols exhibited strong antimicrobial activity against Salmonella, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa and antitumor activity in the human liver cancer HepG2 and SMMC-7721 cell lines. This study highlights the feasibility of recovering CBT-diols from tobacco flower waste using DESs and provides opportunities for potential waste management using green technologies.

Isolation and characterization of dihydrohomoisoflavonoids from Portulaca oleracea L.

Eight pairs of dihydrohomoisoflavonoids (1−8), including four pairs of enantiomeric aglycones [(R,S)-portulacanones B (1) and C (2) and (R,S)-oleracones C (3) and Q (4)] and four pairs of epimeric glycosides [portulacasides A−D and epiportulacasides A−D (5−8)], were obtained from Portulaca oleracea L. Among them, (R,S)-oleracone Q (4) and four pairs of epimeric glycosides (5−8) were reported for the first time. The 50% EtOH fraction from the 70% EtOH extract prevented HepG2 human liver cancer cell damage induced by N-acetyl-p-aminophenol (APAP), and the cell survival rate was 62.3%. Portulacaside B (6a), which was isolated from the 50% EtOH fraction, exhibited hepatoprotective and anti-inflammatory effects. The compound increased the survival rate of APAP-damaged HepG2 human liver cancer cells from 40.0% to 51.2% and reduced nitric oxide production in RAW 264.7 macrophages, resulting in an inhibitory rate of 46.8%.

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.

Novel chiral matrine derivatives as potential antitumor agents: Design, synthesis and biological evaluation

Since the thalidomide incident, research on chiral drugs has escalated immensely. Differences in drug configuration can lead to significant variations in therapeutic efficacy. Matrine, a natural product esteemed for its low toxicity and high water solubility, has garnered significant attention in research endeavors. Nonetheless, its precise target has proven elusive. In this study, we designed and synthesized a novel chiral matrine derivative. Their cytotoxicity against three types of tumor cells was assessed. Comparing the newly synthesized derivatives to the parent matrine, most compounds exhibited significantly enhanced inhibitory effects on cancer cells. Among them, Q12 exhibited the highest activity, with IC50 values of 8.31 μM against rat glioma cells C6, 6.3 μM against human liver cancer cells HepG2 and 7.14 μM against human gastric cancer cells HGC-27, meanwhile showing low toxicity. Based on IC50 values, we constructed a preliminary structure–activity relationship (SAR). Compound Q12 significantly suppressed the cloning and migration of HepG2 cells. Further mechanistic studies indicated that Q12 inhibited Topo I in HepG2 cells, leading to DNA damage, induction of G0/G1 cell cycle arrest and ultimately causing apoptosis. The molecular docking experiments provided a rational binding mode of Q12 with the Topo I-DNA complex. In vivo, experiments demonstrated that Q12 exhibited a higher tumor growth inhibition rate (TGI) compared to the positive control drug Lenvatinib, while maintaining good safety. In summary, it suggests that Topo I might be a potential target for matrine and Q12 represents a promising candidate for cancer treatment.

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

Mesoporous Silicon Nanoparticles with Liver-Targeting and pH-Response-Release Function Are Used for Targeted Drug Delivery in Liver Cancer Treatment.

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Early diagnosis and intervention of Alzheimer’s disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood–brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 μm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

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.

Analysis of gene expression changes during lipid droplet formation in HepG2 human liver cancer cells.

Fatty liver is a condition of excessive triglyceride accumulation in hepatocytes. Additionally, hepatocytes exhibit a high degree of fat droplet accumulation during excessive alcohol consumption and metabolic syndrome. However, the molecular mechanisms involved in fat droplet formation remain unknown. The present study used an in vitro fatty liver formation model of the human liver cancer cell line, HepG2, to comprehensively search for fat droplet formation-related genes, and which exhibit changes in expression during fat droplet formation. Microarray analysis with extracted total RNA determined the genes that are involved in fat droplet formation and their expression was confirmed using quantitative polymerase chain reaction following the culture of the HepG2 cells in culture medium containing 0, 50, 200 and 500 µM of oleic acid for 24 h. The results revealed 142 genes demonstrating increased expression levels by >2.0-fold with oleic acid treatment and 426 genes demonstrating decreased expression levels. Perilipin 2 (PLIN2) was estimated as the gene most closely associated with fatty liver. Lipid droplet formation in the HepG2 cells induced by oleic acid led to the upregulation of PLIN2 in a concentration-dependent manner. On the whole, the findings of the present study indicate the involvement of genes in oleic acid-induced lipid droplet formation in HepG2 cells; PLIN2 in particular may play a crucial role in this process.

Triphala extract Reduces Anti-apoptotic Protein (Mcl-1) Expression through the Activation of Caspase 3 in Hepatocellular Carcinoma Cells

Triphala is an equal mixture of the three myrobalans Terminalia chebula (Haritaki), Terminalia bellerica (Bibhitaki), and Phyllanthus emblica (Amalaki), according to the Ayurvedic Formulary of India. Triphala is an herbal supplement that is high in antioxidants and has a number of advantageous qualities. Numerous investigations conducted in recent years have shown that Triphala has anti-mutagenic and radioprotective properties. Therefore, the aim of the present study was to examine if an ethanolic extract of Triphala had any inhibitory effects on hepatocellular carcinoma cells (HCCs). Gas chromatography-mass spectrometry analysis was used to identify and quantify various phytochemicals in triphala extract (TE). Further, in two human liver cancer cells (HepG2 and Hep3B), TE was examined for its cytotoxic potential by [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Apoptosis was promoted by TE, which also suppressed the production of anti-apoptotic proteins and triggered poly-ADP ribose polymerase cleavage. Significantly, TE has a cytotoxic effect against liver cancer cells. The current study demonstrated that the ethanolic extract of triphala has anticancer properties against HCC. As a result, Triphala may offer a potential alternative to conventional therapy for cancer patients.

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.

In Vitro Screening of Anticancer Activity and Phytochemical of Connarus Wightii Medicinal Plant

Due to the rising death rate from cancer worldwide, it is one of the biggest worries. Globally, medicinal plants have a significant impact on people's health. According to recent research, on the phytochemical analysis of medicinal plant in southern Tamilnadu, particularly in the southwest portion of the Kanayakumari district Thus, the primary goal of this study was to identify the phytochemical compounds, antioxidant properties and anti-cancer properties of medicinal plant connarus wightii. An analysis was conducted on the phytochemical make up of these extracts (chloroform, ethanol, and methanol). Additionally, the extracts from these plants were assessed for their anti-cancer properties. The most prevalent phytochemical components in the plants under investigation were found to be phenols, flavonoids, saponins, glycosides etc, According to recent research, plant extracts have anticancer action of connarus wightii As the result of anticancer investigation using the MTT assay, the test samples, chloroform, ethanol, and methanol extracts of connarus wightii , were strongly cytotoxic to human liver cancer (HepG2) cells with low IC50 values of 99.91, 158.12, and 47.42 µg/ml, respectively. They had an IC50 of less than 10 μg/ml against the cancer cell lines was investigated. This low IC50 suggests that crude extracts have potential as an anticancer drug. The significance of these identified plant species as a source of anticancer drugs was therefore emphasised by the current investigation.

Electrodeposition of gold-platinum nanoparticles on 2D M-TCPP (M = Co, Cu, Zn) for electrochemical monitoring of H2O2 from living cells

Two-dimensional (2D) metal–organic frameworks (MOFs) as supporting nanomaterials to encapsulate or load metal nanoparticles have been widely applied in electrochemical sensing. Therefore, the influences of tetrakis(4-carboxyphenyl) porphyrin-based MOFs (M-TCPP (M = Co, Cu, Zn)) as supporting materials on the electrocatalytic activity were studied. A surfactant-assisted method was employed to facilely synthesize three types of 2D M-TCPP nanosheet MOFs. Polyvinylpyrrolidone was selected as a surfactant for preparing M-TCPP and played a key role in the controlled anisotropic growth of MOF crystals, resulting in the formation of 2D MOF nanosheets. Then, one-step electrodeposition of gold-platinum nanoparticles (AuPt NPs) on the M-TCPP-modified glassy carbon electrode (AuPt/M-TCPP/GCE) was explored for reducing hydrogen peroxide (H2O2). Cyclic voltammetry was applied to investigate the electrocatalytic performance of AuPt/M-TCPP/GCE, and AuPt/Cu-TCPP/GCE exhibited better electrocatalytic characteristics than AuPt/Co-TCPP/GCE and AuPt/Zn-TCPP/GCE. The electrochemical H2O2 sensor displayed a low detection limit of 3.1 nM in the wide concentration range of 0.01 μM to 80 mM. In addition, the proposed sensor showed high stability, good reproducibility, and selectivity. Moreover, HepG2 human liver cancer cells were selected for real-time detection of H2O2 to verify the feasibility of this technology for the evaluation of anticancer drugs. The results showed that Cu-TCPP can be used as an efficient supporting material for enhancing the detection property of electrochemical sensors.

Comprehensive Assessment of the Stability of Selected Coxibs in Variable Environmental Conditions along with the Assessment of Their Potential Hepatotoxicity.

Determining the influence of environmental factors on the stability of drugs is very helpful when choosing excipients, storage conditions or packaging materials. In addition, information about possible toxic degradation products enables detecting and avoiding the harmful side effects of the drug. We used the thin-layer chromatographic-densitometric procedure for the assay of five coxibs, conducted degradation studies in various environments and at different temperatures along with the determination of pharmacokinetic parameters. The results were subjected to chemometric analysis, to investigate and visualize the similarities and differences of the studied coxibs. Samples of the tested drug were also analyzed by UPLC-MS/MS in order to identify degradation products, and determine possible drug degradation pathways. Using the human liver cancer HepG2 cell line, the hepatotoxic effect of the degradation products was also determined. It was observed that all substances were relatively stable under the analyzed conditions and degraded more in acidic than alkaline environments. Robenacoxib is the drug that decomposes the fastest, and cimicoxib turned out to be the most stable. Robenacoxib also showed significant hepatotoxicity at the highest tested concentration, which correlates with the high degree of its degradation, and the probable formation of a more hepatoxic product. The obtained mass spectra of compounds formed as a result of hydrolysis of the protonated drug leading to the formation of several product ions, which enabled us to propose probable degradation pathways.