Liver Cancer Cell Line HepG2 Research Articles

Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.

Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes. In this study, we identified the interaction between O-GlcNAc and β-catenin, and explored their effects on the progression of liver cancer. Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7. In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination. Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells. Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression. In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and β-catenin facilitated the proliferation of liver cancer.

Bioactive glycoalkaloides isolated from Solanum melongena fruit peels with potential anticancer properties against hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is progressively increasing tumor with lack of accurate prognosis and inadequate systemic treatment approaches. Solanum sp. (such as Solanum melongena) is a folk herb which is reported to possess anticancer properties. In a continuity for our interest in pursuing the anticancer activity of compounds isolated from the fruit peels of Solanum melongena, the HPLC profiling and ESI-MS assessment for the methanolic extract evidenced the presence of bioactive glycoalkaloids (solasonine, solasodine and solamargine). These glycoalkaloids were isolated, purified and proved to possess in vitro cytotoxicity against human liver cancer cell lines (Huh7 and HepG2). Herein, we investigated the potential mechanism of action of these compounds using DNA content flow-cytometry and apoptosis/necrosis differential anaylsis using annexin-V/FITC staining. Solasonine, solasodine and solamargine inducd significant antiproliferative effect against liver cancer cells (Huh7 and HepG2) which was attributed to cell cycle arrest at S-phase. Solamargine, solasodine and solasonine induced significant apoptosis in Huh7 cells. Only solamargine-induced cell cycle arrest, was reflected as apoptotic cell killing effect against HepG2 cells. In conclusion, glycoalkaloids derived from Solanum melongena and particularly, solamargine are promising antiproliferative agents with potential anticancer effects.

Treated acid mine drainage and stream recovery: Downstream impacts on benthic macroinvertebrate communities in relation to multispecies toxicity bioassays

The success and long term effectiveness of extensive and expensive engineering solutions to restore streams impacted by Acid Mine Drainage (AMD) is rarely tested. Concentrations of pollutants were measured in water along a longitudinal gradient from a stretch of the Tweelopie stream, South Africa, that receives pH-treated acid mine drainage (AMD) from an abandoned gold mine. The biotoxic effects of treated AMD were determined through macroinvertebrate biotic indices (SASS5) and a battery of toxicity bioassays. These included the L. sativa, A. cepa, D. magna toxicity and Ames mutagenicity tests, as well as an in vitro human liver cancer cell line HepG2. Even though the Tweelopie stream was moderately to severely degraded by multiple anthropogenic stressors, the impact of the treated AMD was masked by the improvement in the system downstream after mixing with the domestic wastewater effluent receiving stream, and subsequent further dilution as a result of the karst springs downstream. The general improvement of the system downstream was clearly shown by the decrease in the ecotoxicity and mutagenicity in relation to the in-stream macroinvertebrates. PCA multivariate analysis successfully displayed associations between the different environmental variables and the decrease in toxicity and subsequent ecosystem improvement downstream. This study indicated that environmental management of AMD remediation should consider long term assessment strategies, including multiple factors, to promote biological ecosystem recovery.

An Approach to Treatment of Liver Cancer by Novel Glycyrrhizin Derivative.

Liver cancer is a life threating disease as it is the fifth most common cancer and the third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment. This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 μM of each compound, cell viability was determined. The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-β-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 μM, respectively. Both the compounds showed higher selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA which might be attributed to its higher activity and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation. This work highlights the cytotoxicity of glycyrrhizin and its derivatives for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18β-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer.

Piloquinone, potent cytotoxic compound from Egyptian Streptomyces pilosus SBG-NRC-216

Background and objective Piloquinone shows biological activity as an anticancer and antitrypanosomal agent, and it acts as an inhibitor for monoamine oxidase, the main causative factor of Alzheimer’s disease. The aim of this study was to produce Piloquinone as a bioactive compound from a local Streptomyces isolate for many medical purposes. Materials and methods Fifty Streptomyces isolates for their capacity of Piloquinone production were tested. The potent Piloquinone producer, SBG-NRC-216 isolate, was identified by conventional and genetic methods. The produced compound was purified and identified on the basis of the spectroscopic analysis. A series of experiments were conducted to investigate efficacy of the compound. Results and conclusion The producer isolate was identified by phenotypic and genotypic methods. These methods confirmed that the strain name was Streptomyces pilosus SBG-NRC-216. The produced compound was purified and identified as Piloquinone. It showed a potent anticancer activity against five different human tumor cell lines: breast cancer cell line MCF-7, human liver cancer cell line HepG2, human lung cancer cell line A549 and human colon cancer cell lines Caco-2 and HCT-116. The results also indicated that Piloquinone had a weak antiviral activity against the H5N1 virus. The results proved that Piloquinone can be used as a bioactive compound that has many industrial and medical purposes.

MRC-5 Cancer-associated Fibroblasts Influence Production of Cancer Stem Cell Markers and Inflammation-associated Cell Surface Molecules, in Liver Cancer Cell Lines.

Background: Current opinion suggests that expansion of cancer stem cells (CSCs) and activation of pro-tumoral inflammation cascade correlate with cancer progression.Materials and methods: We explored the possible contributions of MRC-5 cancer-associated fibroblasts to the expression profiles of CSC markers and inflammation-associated cell surface molecules. The liver cancer cell lines Bel-7402, SMMC-7721, MHCC-LM3, and HepG2 cultured in conditioned medium (CM) from MRC-5 served as test groups, whereas the liver cancer cell lines cultured in normal medium served as control groups.Results: Flow cytometry revealed that the proportions of CD90+ cells were significantly higher in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, and moderately higher in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, than in controls. The CD90+/CD45- proportions were elevated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, but reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, as compared to controls. Western blotting indicated that Nanog was downregulated in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls; that POU5F1 (OCT4/3) was downregulated in MHCC-LM3-(MRC-5)-CM, but upregulated in Bel-7402-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls, and that CK19 was upregulated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, compared to controls. Proportions of cells expressing Toll-like receptor-1+ (TLR1) and TLR4 were significantly higher in MHCC-LM3-(MRC-5)-CM cells, and moderately higher in HepG2-(MRC-5)-CM cells, than controls. However, the TLR1+ and TLR4+ proportions were lower in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells than controls. Proportions of CD25+ cells were reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, but elevated in MHCC-LM3-(MRC-5)-CM and Bel-7402-(MRC-5)-CM cells, compared to controls. Proportion of CD61+ cells was higher in liver cancer cells cultured in MRC-5-CM than in controls. Proportion of CD14+ cells was lower in HCC cells cultured in MRC-5-CM than in controls.Conclusion: MRC-5 extensively affected the production of CSC markers and inflammation-associated cell surface molecules. Tumor-targeting molecular therapies should consider these findings.

Cell cycle arrest and apoptosis in human liver cancer cell line and A549 cell lines by Turbiconol– A novel sterol isolated from Turbinaria conoides

Background: Turbinaria conoides, a brown seaweed, is a rich source of oxygenated fucosterols which are capable of suppressing the proliferation of cancer cells. Their specific therapeutically significant biological activity is directly related to the unique structural features of the molecule. This study specifically focuses on extracting unconventional sterol molecules (side chain extension) from this seaweed which can be used as a lead molecule to evolve therapeutical agents. Materials and Methods: To isolate unconventional sterol molecule, for structural elucidation and bioactivity study, sufficient amount of T. conoides was collected from Mandapam, an unique biodiverse environment along the Southeast coast of India. State-of-the-art methods available for the purification and characterization of molecule (High-resolution fast-atom bombardment mass spectrometry, ultraviolet-visible spectroscopy, attenuated total reflection–fourier transform infra-red, One-dimensional nuclear magnetic resonance, and two-dimensional nuclear magnetic resonance) were put in. In vitro bioassays (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide, double staining, and flowcytometry) were carried out against A549 and human liver cancer cell line (HepG2) malignant cells to assess the cytostatic potential. Data were statistically validated. Results: A unique unconventional sterol molecule (Turbiconol) with ethyl and methyl group at C-27 was isolated. This molecule induced apoptosis in A549 and HepG2. However, cell cycle assessment revealed G0/G1 cell cycle arrest in Hep G2 and G2/M checkpoint was responsible for the suppression of A549 cell line. Conclusion: A novel unconventional compound, turbiconol, is reported in this study. In vitro results highlight the potential of this molecule in developing therapeutical combination which can be used for novel treatment methods.

Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives.

The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3a–c, 7a–c, and 8a–c. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations.

Chloride ions assisted synthesis of tunable gold nanorods: Seedless synthesis, characterization and in vitro toxicity studies

Gold nanorods are interesting due to their capability to absorb light in the near infrared (NIR) wavelength range of 600 nm–1200 nm which is ideal for optical therapeutic imaging. Previous reports in synthesis used cetyltrimethylammonium bromide (CTAB) as capping agent via two-step seed-mediated method done in a laborious manner and major disadvantage is batch to batch variations. To address this issue, we have developed a novel synthetic procedure of synthesizing gold nanorods using cetyltrimethylammonium chloride (CTAC) via seedless, one-step method. The seedless method enables rapid formation of monodisperse gold nanorods with tunable aspect ratios (2–4). Gold nanorods have average lengths in range of 40 nm–55 nm and width of 12 nm–18 nm. Characterization of gold nanorods was done using optical spectroscopy, zeta potential, NTA analysis, FTIR and electron microscopy. Toxicity evaluation of the synthesized CTAC capped gold nanorods was studied on liver carcinoma cell line using MTT assay, Propidium Iodide and Trypan Blue Exclusion assay. The biocompatibility of gold nanorods was evaluated on liver cancer cell line (HepG2) in order to determine their safety using various cytotoxicity assays. We observed a size dependent toxicity of gold nanorods when exposed to liver cancer cells.

3D microdevices that perform sample purification and multiplex qRT-PCR for early cancer detection with confirmation of specific RNAs

MicroRNA expression analysis is an important screening tool for the early detection of cancer. In this study, we developed two portable three-dimensional microdevices for multiple singleplex RNA expression analysis by microRNA purification and qRT-PCR as a prototype for point-of-care testing. These microdevices are composed of several types of modules termed ‘chemical IC chips’. We successfully reduced the heating area and fluorescence observation area, reduced the energy required for the reaction, and improved the portability of all systems in the devices. The purification microdevice could purify the microRNA from the sample using the FTA elute card system. The disposable reactor module mounted on both devices was easily fabricated by deforming a 100-μm-thick polypropylene film using an uncomplicated procedure. The qRT-PCR microdevice could perform reactions for samples of small volume. We purified microRNA from the HepG2 liver cancer cell line using the purification microdevice and confirmed the expression level of miR-224, which is a potential biomarker for liver cancer. Furthermore, we observed an increase in the fluorescence intensity when we performed qRT-PCR in the qRT-PCR microdevice. Therefore, the two developed microdevices show promise as a new portable tool for early cancer detection.

Cucurbitane triterpenoids from the fruit of Momordica charantia L. and their anti-hepatic fibrosis and anti-hepatoma activities

Momordica charantia L. (Cucurbitaceae) is a popular vegetable and traditional folk medicine, that has been used for hundreds of years. In this study, three undescribed cucurbitane-type triterpene glycosides furpyronecucurbitane A, goyaglycoside I and charantagenin F along with nine known compounds were isolated from the immature fruit of Momordica charantia L. Their structures were identified on the basis of extensive 1D, 2D NMR and HRESIMS spectroscopy analysis. All isolated compounds were examined for their anti-hepatic fibrosis activity against murine hepatic stellate cells (t-HSC/Cl-6) and anti-hepatoma activity against two kinds of liver cancer cell lines (HepG2 and Hep3B). Among them, karaviloside III exhibited excellent inhibitory activity against activated t-HSC/Cl-6 cells and cytotoxic activity against Hep3B and HepG2 cell lines with IC50 values of 3.74 ± 0.13, 16.68 ± 2.07 and 4.12 ± 0.36 μM, respectively, which may potential to be developed as a chemotherapy agent for treatment hepatic fibrosis or carcinoma and protection against both diseases.

Efficient drug delivery of 5-fluorouracil by a biocompatible Zn-metal–organic framework nanostructure and anti-liver cancer activity study

Porous metal–organic frameworks (MOFs) are structures made up of inorganic nodes and organic ligands, which can be used as crystalline vessels to accommodate various functional guests. This study reports on the drug delivery of a new porous metal–organic framework [Zn3(BTC)2(Aml)(H2O)2](MeOH)6 (1, H3BTC = 1,3,5-benzenetricarboxylic acid, Aml = ammeline). The Zn-MOF nanocomposites were synthesized by reaction of Zn(NO3)2·6H2O and the organic ligand with the aid of polyvinyl pyrrolidone. Stability and porosity of this nanostructure have been confirmed via the PXRD measurement and gas sorption studies. Due to its large BET surface areas, suitable window size, and high density of open free N sites, this MOF has been used for the anticancer drug 5-fluorouracil (5-Fu) storage/delivery, a moderate–high 5-Fu loading capacity, and pH-dependent drug release behavior which could be observed. Furthermore, the in vitro cytotoxicity of the nano-1 and the 5-Fu@nano-1 composite toward the human normal fibroblastic epithelial cell line (HFL1) and human liver cancer cell line HepG2 has been evaluated via the MTT assay.

Investigation of the antimicrobial and anticancer activity of aminonaphthoquinones.

In this study, we report on the inhibitory activity of synthesized aminonaphthoquinones against two bacterial and one fungal species to determine their antimicrobial properties. A minimum inhibitory concentration (MIC) of 7.8 μg/mL was obtained against the fungus, Candida albicans, which was better than that of Amphotericin B (MIC = 31.25 μg/mL). Escherichia coli (Gram -), was inhibited at a MIC of 23.4 μg/mL and Staphylococcus aureus (Gram +) at a MIC of 31.3 μg/mL. The aminonaphthoquinones were also screened against HCT116 colon, PC3 prostate and HepG2 liver cancer cell lines to evaluate their cytostatic effects. They had potent activity (GI50 = 5.87-9.90 μM) which was about three-6-fold better than that of parthenolide (GI50 = 25.97 μM) against the prostate cancer cell line. These compounds were generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI-38).

Genistein-triggered anticancer activity against liver cancer cell line HepG2 involves ROS generation, mitochondrial apoptosis, G2/M cell cycle arrest and inhibition of cell migration.

IntroductionLiver cancer is one of the most common malignancies across the globe and one of the major causes of cancer-related mortality. With limited available treatment options, there is an urgent need to look for new available options. Genistein is an important plant flavonoid and has been shown to possess tremendous pharmacological potential. The objective of the present study was therefore to evaluate the anticancer effect of the genistein.Material and methodsThe antiproliferative activity and IC50 of genistein were determined by MTT assay. Reactive oxygen species (ROS) and cycle distribution were investigated by flow cytometry. Apoptosis was detected by DAPI and annexin V/IP staining. Cell migration was investigated by wound healing assay. Protein expression was estimated by western blotting.ResultsMTT assay revealed that genistein reduced the cell viability of HepG2 cancer cells in a dose-dependent manner. Genistein also reduced the colony forming potential of the HepG2 cell concentration dependently. The IC50 of genistein was found to be 25 μM. Genistein caused G2/M cell cycle arrest and G2/M cells increased from 4.2% in the control to 56.4% at 100 μM concentration. Genistein prompted generation of significant (p < 0.01) amounts of ROS, ultimately favouring cell death. Genistein also triggered apoptosis which was associated with upregulation of cytosolic cytochrome c, Bax, cleaved caspase 3 and 9 expression and downregulation of Bcl-2 expression in HepG2 cells.ConclusionsWe propose that genistein exhibits significant anticancer activity against liver cancer and therefore may prove beneficial in the management of liver cancer.

Evaluation of genotoxic potential of tert-butylquinone and its derivatives in prokaryotic and eukaryotic test models

Tert-butylquinone (TBQ) and its alkylamino and aralkylamino derivatives are of high interest as a potential antitumor agent. Therefore, it was necessary to investigate if the compounds exert undesirable activities such as interaction with DNA molecule which could result in negative side effects in the case of their use in the diseases treatment. The major aim of this study was to investigate genotoxic potential of TBQ and selected derivatives in an acellular model by using plasmid DNA, in the prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002 and in eukaryotic models by using comet assay in human fetal lung cell line (MRC-5) and human liver cancer cell line (HepG2). Results indicated that in the acellular model TBQ and its derivatives do not interact with plasmid pUC19. In the prokaryotic model, only TBQ exerted weak genotoxic potential and only at highly cytotoxic concentrations. In eukaryotic models, genotoxic potential was detected mainly at the highest concentrations of the tested substances but the effect was lower in both cell lines in comparison with benzo[a]pyrene and etoposide which were used as positive controls. Weak genotoxic potential of tested compounds recommends them as good candidates for further testing in development of new antitumor agents.

Design, synthesis and biological evaluation of a novel library of antimitotic C2-aroyl/arylimino tryptamine derivatives that are also potent inhibitors of indoleamine-2, 3-dioxygenase (IDO)

A novel library of C2-substituted tryptamines (based on diverse C2-aroyl/arylimino indoles and indole-diketopiperazine hybrids) possessing antimitotic properties were designed, synthesized and screened for their inhibitory activity against tubulin polymerization, and against proliferation of A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines. The design of molecules were inspired from known antimitotic compounds and natural products. The molecular docking of the designed compounds indicated that they bind to the colchicin binding site of tubulin. They were synthesized by a unique iodine catalysed oxidative ring opening reaction of 1-aryltetrahydro-β-carbolines. Among the compounds synthesized quite a few compounds induced cytotoxicity on the cancer cells by disrupting the tubulin polymerization. They were found to be non-toxic for healthy cells. Immuno Fluorescence study for the most active molecules (between ~6 μM concentration) against A549 and HeLa cells demonstrated complete disruption and shrinkage of the microtubule structures. These compounds also inhibited indoleamine-2, 3-dioxygenase with low micromolar IC50.

Phenotypic and functional characterization of tumor-derived endothelial cells isolated from primary human hepatocellular carcinoma.

Tumor endothelial cells (TECs) have been investigated using human tumor xenografts in mice models. In order to provide pure human TECs for the updating of clinical anti-angiogenic cancer therapy, in the present study we established a protocol of purification of TECs derived from clinical hepatocellular carcinoma (HCC) and revealed the TEC features by in vitro and in vivo assays. We isolated TECs from fresh surgical resections of HCC by magnetic-activated cell sorting and purified by flow cytometry sorting upon CD31 expression, referred to as ECDHCCs. Next, we identified cultured ECDHCCs by morphology, phenotype, genotype, and functional assays. The ECDHCCs appeared as Weibel-Palade bodies under electron microscopy. They expressed endothelial markers, such as CD31, CD105, and vascular endothelial growth factor receptor 2, and expressed the genes that are associated with pro-angiogenesis, especially vascular endothelial growth factor, epiregulin, and programmed cell death 10. Functionally, ECDHCCs were capable of tube formation, wound healing, and Transwell migration in vitro. These in vitro behaviors were validated by in vivo Matrigel plug assay in mice. Finally, comparison of ECDHCC with the Hep-G2 liver cancer cell line showed there was no similarity of phenotype or function between these two types of cells. Tumor endothelial cells derived from human HCC can be isolated and purified from clinical samples by flow cytometer. They have the endothelial phenotype and morphologic features and are capable of tube formation and migration. This study provides a useful model for researchers to study tumor angiogenesis and screening of candidate targets.

MicroRNA-146a-5p enhances ginsenoside Rh2-induced anti-proliferation and the apoptosis of the human liver cancer cell line HepG2.

Liver cancer is one of the leading causes of malignancy-associated mortality worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2 (Rh2) has been reported to have antitumor effects on some types of cancer, including liver cancer. However, its regulatory mechanism has not been extensively evaluated. In the present study, Rh2 increased the expression of microRNA (miR)-200b-5p, miR-224-3p and miR-146a-5p, and decreased the expression of miR-26b-3p and miR-29a-5p. Of the three upregulated miRs, miR-146a-5p exhibited the highest fold elevation. In accordance with a previous study, Rh2 effectively inhibited the survival of liver cancer cells in vitro and in a mouse model. In addition, it was observed that Rh2 markedly promoted liver cancer apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of cell survival as well as colony formation induced by Rh2 were enhanced and weakened by miR-146a-5p overexpression and inhibition, respectively. The results of the present study provide further evidence of the antitumor effect of Rh2 in liver cancer and also demonstrate that this effect may be mediated via the regulation of miR-146a-5p expression in the liver cancer cell line HepG2. The results indicated that miR-146a-5p may be a promising regulatory factor in Rh2-mediated effects in liver cancer.

Metabolic Network-Based Identification and Prioritization of Anticancer Targets Based on Expression Data in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with high mortality worldwide. Unfortunately, the large heterogeneity of this disease makes it difficult to develop effective treatment strategies. Cellular network analyses have been employed to study heterogeneity in cancer, and to identify potential therapeutic targets. However, the existing approaches do not consider metabolic growth requirements, i.e., biological network functionality, to rank candidate targets while preventing toxicity to non-cancerous tissues. Here, we developed an algorithm to overcome these issues based on integration of gene expression data, genome-scale metabolic models, network controllability, and dispensability, as well as toxicity analysis. This method thus predicts and ranks potential anticancer non-toxic controlling metabolite and gene targets. Our algorithm encompasses both objective-driven and—independent tasks, and uses network topology to finally rank the predicted therapeutic targets. We employed this algorithm to the analysis of transcriptomic data for 50 HCC patients with both cancerous and non-cancerous samples. We identified several potential targets that would prevent cell growth, including 74 anticancer metabolites, and 3 gene targets (PRKACA, PGS1, and CRLS1). The predicted anticancer metabolites showed good agreement with existing FDA-approved cancer drugs, and the 3 genes were experimentally validated by performing experiments in HepG2 and Hep3B liver cancer cell lines. Our observations indicate that our novel approach successfully identifies therapeutic targets for effective treatment of cancer. This approach may also be applied to any cancer type that has tumor and non-tumor gene or protein expression data.

RETRACTED ARTICLE: Two New Co(II)-Cluster-Based Coordination Polymers Based on the C3-Symmetrical Organic Ligand: Synthesis, Crystal Structures and Anti-Liver Cancer Activity

In this work, two new Co(II)-cluster-based coordination polymers have been obtained via a one pot solvothermal reaction of Co(NO3)2·6H2O with two similar C3-symmetrical polycarboxylic acid organic ligands with or without auxiliary organic ligands, which reveal different framework dimensionality. The compound 1 with the chemical formula of [Co3(NTB)2(bpy)2](DMA)2 (byp = 4,4′-bipyridine, H3NTB = 4,4′,4′′-nitrilotribenzoic acid) is constructed from the linear Co3 cluster which is further extended via the rigid NTB3− and bpy ligands to afford a three-dimensional framework, while complex 2 with the formula of [Co2(HTPA)2(H2O)2](DMA)2 (H3TPA = tris((4-carboxyl)phenylduryl)amine) is built from the binuclear Co(II)-cluster that shows a two-dimensional framework due to partly deprotonation of the carboxylic groups of the H3TPA ligand. Furthermore, the in vitro anticancer activity was then evaluated against human liver cancer cell lines HepG2 via the MTT assay.