Human Liver Cancer Research Articles

Development of fatty liver disease model using high cholesterol and low choline diet in white leghorn chickens

Nonalcoholic fatty liver disease (NAFLD), which shows similar symptoms as fatty liver hemorrhage syndrome (FLHS) in chickens, is the most common cause of chronic liver disease and cancer in humans. NAFLD patients and FLHS in chickens have demonstrated severe liver disorders when infected by emerging strains of human hepatitis E virus (HEV) and avian HEV, respectively. We sought to develop a fatty liver disease chicken model by altering the diet of 3-week-old white leghorn chickens. The high cholesterol, and low choline (HCLC) diet included 7.6% fat with additional 2% cholesterol and 800 mg/kg choline in comparison to 5.3% fat, and 1,300 mg/kg choline in the regular diet. Our diet induced fatty liver avian model successfully recapitulates the clinical features seen during NAFLD in humans and FLHS in chickens, including hyperlipidemia and hepatic steatosis, as indicated by significantly higher serum triglycerides, serum cholesterol, liver triglycerides, cholesterol, and fatty acids. By developing this chicken model, we expect to provide a platform to explore the role of lipids in the liver pathology linked with viral infections and contribute to the development of prophylactic interventions.

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling.

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1D NMR (1H- and 13C NMR and APT), 2D NMR (HETCOR and HMBC), and elemental analysis. All compounds (1-15) were tested in human lung (A549) and liver (HepG2) cancer cell lines for 72 h. The compounds were screened against a healthy embryonic kidney cell line (HEK-293T) under the same conditions to determine their toxic effects. According to the results obtained, one of the compounds, in particular, compound 8 was effective at inhibiting the growth of cancerous cells, and its effects on both cancer cell lines were similar to IC50 values of 42.43 and 48.43 μM for A549 and HepG2, respectively. Compound 8, which was determined to be the best anticancer agent in vitro, was chosen to interact with the target via molecular docking. This selected ligand (compound 8) interacted with the targets 4HJO, 4ASD, 3POZ, and 7TZ7, and docked into the active sites. The docking score, Glide energy, and Glide emodel values were calculated and determined to be lower than those of the reference compound cisplatin. The pharmacokinetic properties, stability, and drug-likeness parameters of all designed compounds were estimated using SwissADME. Finally, the binding affinities of compound 8 for all four targets were calculated using the MM-GBSA method.

Tethering of hexokinase 2 to mitochondria promotes resistance of liver cancer cells to natural killer cell cytotoxicity.

Hexokinases (HKs) control the first step of glucose catabolism. A switch of expression from liver HK (glucokinase, GCK) to the tumor isoenzyme HK2 is observed in hepatocellular carcinoma progression. Our prior work revealed that HK isoenzyme switch in hepatocytes not only regulates hepatic metabolic functions but also modulates innate immunity and sensitivity to Natural Killer (NK) cell cytotoxicity. This study investigates the impact of HK2 expression and its mitochondrial binding on the resistance of human liver cancer cells to NK-cell-induced cytolysis. We have shown that HK2 expression induces resistance to NK cell cytotoxicity in a process requiring mitochondrial binding of HK2. Neither HK2 nor GCK expression affects target cells' ability to activate NK cells. In contrast, mitochondrial binding of HK2 reduces effector caspase 3/7 activity both at baseline and upon NK-cell activation. Furthermore, HK2 tethering to mitochondria enhances their resistance to cytochrome c release triggered by tBID. These findings indicate that HK2 mitochondrial binding in liver cancer cells is an intrinsic resistance factor to cytolysis and an escape mechanism from immune surveillance.

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.

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.

Biosynthesis of Ag nanoparticles using Laurus nobilis leaf extract and biomedical applications

The green synthesis of metallic nanoparticles using plant extracts is attracting increasing attention as it is cost-effective, environmentally friendly, and suitable for large-scale production. Phytochemicals in plant extracts are used to reduce and stabilize metal nanoparticles. This study highlights the synthesis of silver nanoparticles (Ag NPs) at room temperature using Laurus nobilis (L. nobilis) leaf extract and their antibacterial and cytotoxic activities for biomedical applications. Ag nanoparticles (Ag NPs) were synthesized using L. nobilis leaf extract via the green approach. The synthesized Ag NPs were characterized by UV–Visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscope (SEM), Fourier transform infrared, and X-ray diffraction (XRD) analysis. According to TEM, SEM, and XRD diffraction analysis, it was found that the synthesized Ag NPs have a face-centered cubic crystal structure with a mean particle size of 13 ± 4 nm. The synthesized Ag NPs were tested for their in vitro antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The minimum inhibition concentration (MIC) and minimum bactericidal concentration values of Ag NPs were 3.5, 0.45, and 7, 0.9 μg/mL, respectively. The synthesized Ag NPs were screened toward the human liver cancer cell line in vitro. The results show that the Ag NPS synthesized using L. nobilis leaf had high cytotoxic activity with an IC50 value of 8.86 ± 0.74 µL/mL.

SHOC2 plays an oncogenic or tumor-suppressive role by differentially targeting the MAPK and mTORC1 signals in liver cancer

Abstract SHOC2 is a scaffold protein that activates the RAS-MAPK signal. Our recent study showed that SHOC2 is also a negative regulator of the mTORC1 signal in lung cancer cells. Whether and how SHOC2 differentially regulates the RAS-MAPK vs. the mTORC1 signals in liver cancer remains unknown. Here, we showed that SHOC2 is overexpressed in human liver cancer tissues, and SHOC2 overexpression promotes the growth and survival of liver cancer cells via activation of the RAS-MAPK signal, although the mTORC1 signal is inactivated. SHOC2 knockdown suppresses the growth of liver cancer cells mainly through inactivating the RAS-MAPK signal. Thus, in the cell culture models, SHOC2 regulation of growth is dependent of the RAS-MAPK but not the mTORC1 signal. Interestingly, in a mouse liver cancer model induced by diethylnitrosamine (DEN)-high-fat diet (HFD), hepatocyte-specific Shoc2 deletion inactivates the Ras-Mapk signal but has no effect in liver tumorigenesis. However, in the Pten loss-induced liver cancer model, Shoc2 deletion further activates mTorc1 without affecting the Ras-Mapk signal and promotes liver tumorigenesis. Collectively, it appears that SHOC2 could act as either an oncogene (via activating the MAPK signal) or a tumor suppressor (via inactivating the mTORC1 signal) in the manner dependent of the dominancy of the MAPK vs. mTORC1 signals.

Triterpenes from antler-shaped fruiting body of Ganoderma lucidum and their hepatoprotective activities

Seven previously undescribed triterpenes (1–7), as well as one triterpene (8) previously described as a synthetic product, were isolated from the antler-shaped fruiting body of Ganoderma lucidum. Their structures were established based on comprehensive spectroscopy analysis. At a concentration of 10 μM, (24E)-3-oxo-15α-acetoxy-lanosta-7,9(11),24-trien-26-al (3) and (24R,25S)-3-oxo-lanosta-7,9(11)-dien-25-ethoxyl-24,26-diol (5) provided significant protection against acetaminophen-induced necrosis in human HepG2 liver cancer cells, and the cell survival rates were 69.7 and 76.1% respectively, similar to that of the positive control (glutathione, 72.1%). Based on the present results, these compounds could be potential hepatoprotective agents.

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

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.

Autophagy-induced cell death by aqueous and polyphenol-enriched extracts of honeybush (Cyclopia spp.) inliver and colon cancer cells.

The anti-cancer potential of Cyclopia species (honeybush) has been demonstrated in several models. The present study investigated the effects of aqueous and polyphenol-enriched (PE) extracts of C. subternata and C. genistoides, as well as mangiferin and hesperidin, on different cell growth parameters in human liver (HepG2) and colon (HT-29) cancer cells. Mangiferin and hesperidin were most abundant in C. genistoides and C. subternata, respectively. Cyclopia subternata extracts had the highest ferric-reducing antioxidant capacity. Following exposure of the cells to the extracts and compounds, cell viability, proliferation, and death (apoptosis and autophagy) were determined. Cyclopia subternata extracts reduced cell viability and inhibited cell proliferation the most, associated with depletion of ATP. In HepG2 cells, the PE extracts were less effective than the aqueous extracts in reducing cell viability but more effective in inhibiting cell proliferation. Despite disrupting cell growth, none of the extracts induced apoptosis. The aqueous extracts affected autophagy in both cancer cells. Disruption of mitochondrial membrane integrity by the different extracts, presumably via polyphenol/iron interactions, is postulated to be involved; however, mangiferin and hesperidin had no effect, suggesting that other polyphenols and/or complex interactions between compounds are likely responsible for the differential cytotoxic and/or cytoprotective effects of the extracts.

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.

Microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug.

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations.

Estrogen Induces LCAT to Maintain Cholesterol Homeostasis and Suppress Hepatocellular Carcinoma Development.

Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth-promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC. Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.

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.

Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer.

The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.

Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis.

The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.

Ribosome-inactivating Protein MAP30 Isolated from Momordica Charantia L. Induces Apoptosis in Hepatocellular Carcinoma Cells.

Ribosome-inactivating proteins (RIPs) have been reported to exert antitumor and anti-virus activities. A recent patent CN202011568116.7 has developed a new method to prepare Momordica anti-HIV protein of 30 kDa (MAP30). MAP30 is a type I RIP, which kills various tumor cells through the N-glycosidase activity and irreversibly inhibits protein synthesis. To assess the potential role of MAP30 in inducing apoptosis of human hepatocellular carcinoma HCC-LM3 cells and elucidate the molecular mechanism of MAP30. CCK-8 assay was used to assess the proliferation of HCC-LM3 cells. Flow cytometry was used to measure the cycle, the level of ROS and apoptosis in HCC-LM3 cells. Western blots was used to measure protein levels. Treatment with MAP30 reduced survival and proliferation of human liver cancer HCCLM3 cells in a dose-dependent manner. PI staining showed cell cycle arrest in G0/G1 phase. Furthermore, MAP30 increased the level of ROS in HCC-LM3 cells in 24 h treatment. To further confirm the role of MAP30 in inducing cell apoptosis, immunoblotting was carried out to detect the change of apoptosis-related proteins including PARP poly (ADP-ribose) polymerase (PARP- 1), Casepase3 and Cleaved-Caspase9. We found that PARP-1 and Caspase-3 were downregulated, whereas Cleaved-Caspase9 was up-regulated in HCC-LM3 cells treated with MAP30. This study indicated that MAP30 has the potential to be a novel therapeutic agent for human hepatocellular carcinoma.

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.