Human Liver Cancer Cells HepG2 Research Articles

Flavonoids of Rosa rugosa Thunb. inhibit tumor proliferation and metastasis in human hepatocellular carcinoma HepG2 cells

Rosa rugosa Thunb. is recognized as both medicine and edible in China. The article investigated the antitumor activity of rose flavonoids. Water-extracted rose flavonoids (RFW) and ethanol-extracted rose flavonoids (RFE) were achieved by extracting with distilled water and 70% ethanol, respectively. The effects of the two extracts on proliferation inhibition, apoptosis inducement and metastasis prevention of human HepG2 hepatocellular carcinoma cell lines were tested, via optical/fluorescence microscopy, MTT detection, Transwell assay, flow cytometry and Western blot, etc. The results indicated that rose flavonoids at low concentration (10–40μg/mL) had a better inhibitory effect on migration and invasion of HepG2 cells in a dose-dependent manner, while rose flavonoids at high concentration (80–160μg/mL) could induce apoptosis of HepG2 cells by up-regulating the expression of pro-apoptotic proteins p53 and Bax, and down-regulating the expression of anti-apoptotic proteins Bcl-2, leading to the functioning of caspase-3 and caspase-9. The effect of RFE at the same concentration was significantly better than that of RFW. Conclusion, this study found that rose flavonoids had a certain inhibitory effect on proliferation and metastasis of human liver cancer cells HepG2, indicating the application of rose flavonoids in preventing and treating of liver cancer.

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies.

Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatography–mass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by β-(E)-ocimene (11.80%), D-limonene (8.08%), β-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC50 value of 38.15 ± 2.09 µg/mL. In addition, it effectively inhibited acetylcholinesterase with an IC50 value of 32.9 ± 2.1 µg/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC50 values of 57.80 ± 3.30 and 274.03 ± 12.37 µg/mL, respectively. The molecular docking studies revealed that (E)-β-caryophyllene, one of the major compounds, achieved the best docking scores of −6.75, −5.61, and −7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose.

CuCo-Cu@CoCH stamen-like nanoarray prepared by co-reduction for electrochemical detection of hydrogen peroxide

Accurate and convenient detection of H2O2 is of great significance for the diagnosis and treatment to some diseases. Herein, a unique stamen-like CuCo-Cu@Co(CO3)0.5(OH) (defined as CuCo-Cu@CoCH) nanoarray was fabricated by cation exchange and co-reduction for electrochemical detection of H2O2. The nanostructure with large electrochemical surface area can adsorb H2O2 efficiently, while the Cu@CoCH nanowire offers a high-way for electron transfer, and the CuCo nanoparticle possesses high activity for H2O2 reduction. Hence, the CuCo-Cu@CoCH nanoarray performs excellently as a electrochemical H2O2 sensor with a high sensitivity of 3570 μA mM−1 cm−2 (1 μM to 100 μM) and 3290 μA mM−1 cm−2 (100 μM to 2000 μM), a fast response time (＜1.5 s), a low detection limit (0.97 μM, S/N = 3) and superior selectivity, stability. Furthermore, the nanoarray shows promising electrochemical activity for real-time detection of H2O2 released from HepG2 human liver cancer cells. This work offers a novel material as electrochemical sensor to H2O2 with enhanced performance, and shows a new solution to prepare nanostructure of alloy.

Thioether-Based Polymeric Micelles with Fine-Tuned Oxidation Sensitivities for Chemotherapeutic Drug Delivery.

Oxidation-sensitive drug delivery systems (DDSs) have attracted attention due to the potential to improve efficacy and safety of chemotherapeutics. These systems are designed to release the payload in response to oxidative stress conditions, which are associated with many types of cancer. Despite extensive research on the development of oxidation-sensitive DDS, the lack of selectivity toward cancer cells over healthy cells remains a challenge. Here, we report the design and characterization of polymeric micelles containing thioether groups with varying oxidation sensitivities within the micellar core, which become hydrophilic upon thioether oxidation, leading to destabilization of the micellar structure. We first used the thioether model compounds, 3-methylthiopropylamide (TPAM), thiomorpholine amide (TMAM), and 4-(methylthio)benzylamide (TPhAM) to investigate the effect of the chemical structures of the thioethers on the oxidation by hydrogen peroxide (H2O2). TPAM shows the fastest oxidation, followed by TMAM and TPhAM, showing that the oxidation reaction of thioethers can be modulated by changing the substituent groups bound to the sulfur atom. We next prepared micelles containing these different thioether groups within the core (TP, TM, and TPh micelles). The micelles containing the thioether groups with a higher oxidation sensitivity were destabilized by H2O2 at a lower concentration. Micelle destabilization was also tested in human liver cancer (HepG2) cells and human umbilical vein endothelial cells (HUVECs). The TP micelles having the highest oxidation sensitivity were destabilized in both HepG2 cells and HUVECs, while the TPh micelles, which showed the lowest reactivity toward H2O2, were stable in these cell lines. The TM micelles possessing a moderate oxidation sensitivity were destabilized in HepG2 cells but were stable in HUVECs. Furthermore, the micelles were loaded with doxorubicin (Dox) to evaluate their potential in drug delivery applications. Among the micelles, the TM micelles loaded with Dox showed the enhanced relative toxicity in HepG2 cells over HUVECs. Therefore, our approach to fine-tune the oxidation sensitivity of the micelles has potential for improving therapeutic efficacy and safety of drugs in cancer treatment.

Designing of an Adipic acid bridged Zn(II) coordination polymer: Synthesis and biological study

♦Adipic acid bridged Zn(II) CP has been designed and synthesised . ♦Supramolecular assembly is constructed through H-bonding and π—π interaction. ♦Antibacterial activities have been performed against E. coli and S. aureus . ♦Anticancer activity of CP has exhibited satisfactory result. ♦Density Functional Theory (DFT) is used to explain electronic properties of CP. In the structure of [Zn(ppmh)(adp)(H 2 O)] n [adp 2− , adipate ion; ppmh, N-Pyridin-2-yl-N'-pyridin-4-ylmethylene-hydrazine], Zn(II) is bridged by dicarboxylato-O of two independent adp 2− and ppmh is affixed through pyridyl-N and water coordinates to form ZnO 3 N tetrahedral coordination motif. The H-bonding and π—π interactions with pendant ppmh help to construct a 3-D supramolecular network. The optical band gap, 3.22 eV, is lower than that of DFT computed energy gap, 3.71 eV which may be due to not inclusion of framework strain in the calculation. The compound shows antibacterial activity [IC 50 , 186 ± 2.1 µg/mL ( E. coli ) and IC 50 , 190.12 ± 2.64 µg/mL ( S. aureus )] and active against HepG2 (Human Liver) cancer cells [LD 50 , 58 µg/mL].

Cytotoxicity and apoptosis response of hexagonal zinc oxide nanorods against human hepatocellular liver carcinoma cell line

Hexagonal zinc oxide nanorods (ZnO-NRs) were prepared via solution process using zinc nitrate hexahydrate (Zn(NO3)2·6H2O, 0.25 M), hexamethylenetetramine (HMT) and sodium hydroxide at low concentration (4 × 10-3 M in 100 ml of distilled water) and refluxed at 100 °C for an hour. The HMT was used because its act as a template for the nucleation and growth of zinc oxide nanorods. The X-ray diffraction patterns (XRD) clearly reveal that the grown product is pure zinc oxide. The diameters and lengths of the synthesized nanorods lie between 200 and 250 nm and 2–3 μm respectively as observed from the field emission scanning electron microscopy (FESEM). The chemical functional properties was analyzed by Fourier Transform infra-red (FTIR) spectroscopy. This study was designed to show the possible effect of ZnO-NRs in human liver cancer (HepG2) cells. It induces cytotoxicity via reactive oxygen species (ROS), mitochondrial membrane potential. For gene expression analysis, it induces apoptotic gene marker P53, Bax, caspase3, Bcl2 genes. Based on analysis and observations, it concludes that the ZnO-NRs were utilized for toxicity at dose dependent via ROS generation against human hepato cellular liver carcinoma cell line.

A Titanium (IV)-Dithiophenolate Complex and Its Chitosan Nanocomposite: Their Roles towards Rat Liver Injuries In Vivo and against Human Liver Cancer Cell Lines.

Titanium (IV)–dithiophenolate complex chitosan nanocomposites (DBT–CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl4) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT–CSNPs and DBT treatments abolished liver damage induced by CCl4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT–CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT–CSNPs were more efficient than DBT. Low doses of DBT and DBT–CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT–CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT–CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT–CSNPs are more efficient. Both compounds can be used in pharmacological fields.

Precise Detection and Visualization of Cyclooxygenase-2 for Golgi Imaging by a Light-Up Aggregation-Induced Emission-Based Probe

Precise Detection and Visualization of Cyclooxygenase-2 for Golgi Imaging by a Light-Up Aggregation-Induced Emission-Based Probe

The Synthesis of Conjugated Peptides Containing Triazole and Quinolone-3-Carboxamide Moieties Designed as Anticancer Agents.

Background: Cancer is a major health concern in human populations worldwide, and due to its causes being multi-factorial, it is not easily curable. Many attempts have been made to tackle this disease in hopes of finding effective anticancer agents which are not harmful to healthy tissues. Peptides with several medicinal activities have been shown to be good candidates as anticancer agents to replace common classic anticancer drugs. Peptides in conjugation with either biologically active heterocyclic compounds or anticancer drugs may result in new molecules compiling the biological benefits of both individual compounds within a unit structure.Objective: In this study some triazole-peptide conjugates as well as ciprofloxacin-peptide conjugates were designed, synthesized, and their anticancer activities evaluated. A normal skin cell line, NIH3, was also employed to determine the safety profiles of these conjugates.Materials and Methods: Two peptides; YIGSR and LSGNK were synthesized by the solid phase peptide synthesis (SPPS) method using Wang resin. Cell viability was examined by employing the MTT assay. To determine the cytotoxicity of the triazole and ciprofloxacin conjugates, two human cancer cell lines were employed; HepG2 (human liver cancer cell line) and LNCaP (human prostatic carcinoma cell line). A human skin fibroblast cell line was also included for comparison.Results: MTT results showed that all the compounds could inhibit the viability of cancerous cells in a concentration- dependent manner.Conclusions: The results showed that these peptide conjugates are toxic against the aforementioned cancerous cells and thus may raise a hope for finding new anticancer agents made by such strategy in the near future.

The effects of quorum sensing molecule farnesol on the yield and activity of extracellular polysaccharide from Grifola frondosa in liquid fermentation

A strategy by exogenous addition of quorum sensing molecule farnesol to improve the production, antioxidant activity and antitumor activity of extracellular polysaccharide (EPS) of Grifola frondosa by liquid fermentation was proposed in the study. The highest yield of EPS induced by farnesol was 1.25 g/L, which was 150% higher than that of the control. Four polysaccharides including EPS-C-0M, EPS-C-0.2M, EPS-F-0M and EPS-F-0.2M were extracted and purified under the conditions of control and farnesol respectively. The physicochemical properties, antioxidant activities and antitumor activities were studied. Their chemical composition differed in sugar, protein and uronic acid contents, and they were composed of six constituent monosaccharides with different ratios, with the average molecular weights of 1.12 × 103, 1.89 × 103, 1.41 × 103 and 2.02 × 103 kDa, respectively. They presented similar FT-IR spectra, but different surface morphology. Antioxidant experiments showed that they had strong scavenging activities on ABTS+, hydroxyl radical, O2− and DPPH radical. Antitumor experiments showed that they had strong inhibitory effects on human cervical cancer (HeLa) cells and human liver cancer cells (HepG2) cells. Among the four polysaccharides, EPS-F-0.2M showed the highest antioxidant and antitumor activities, indicating that farnesol could regulate the biological activity of EPS by affecting structure and properties. These results demonstrated that appropriate adjustment of culture conditions had potential application in the development of polysaccharides with high antioxidant and antitumor activity. It provided a new strategy to enhance the production and bioactivity of edible and medicinal fungal polysaccharides by using quorum sensing molecules.

Combating liver cancer through GO-targeted biomaterials

Hydroxycamptothecin (HCPT) is a topoisomerase I inhibitor, and it has been widely used clinically in the treatment of primary liver cancer, gastric cancer, and other tumors. The clinical application of HCPT is limited by its water solubility, and it has certain toxicity to patients with tumor. Therefore, the effective tumor site accumulation of HCPT is necessary. This work studied the inhibitory effect of HCPT on the proliferation and migration of human liver cancer cells (HepG-2) and used carboxymethyl chitosan (CMC) and hyaluronic acid (HA) to modify graphene oxide (GO) as nano-carrier materials, which load HCPT to achieve a drug delivery system for liver tumors with good biocompatibility and high drug loading. HCPT can significantly inhibit proliferation and migration of HepG-2, enhance the release of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The GO-CMC-HA/HCPT drug delivery system enabled HepG-2 to uptake more HCPT, thereby inhibiting its proliferation and improving the efficacy of HCPT in vivo and in vitro. This study explored a potential therapy strategy by preparing a GO-based tumor-targeted drug delivery system.

Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

The quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde (DPQC) and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline) (MDBD) were synthesized using direct condensation methods, and various spectral analysis were characterized by experimental and ab initio Density functional theory (DFT) theoretical methods at the B3LYP level with 6–311++G(d,p) basis sets were used for the different spectrum analysis, which included UV-Visible, Fourier-transform infrared spectroscopy (FTIR), and 1H and 13C nuclear magnetic resonance (NMR) chemical shifts. Furthermore, for these title molecules, Nonlinear Optical (NLO) was utilized to compute first-order hyperpolarizability (β) and Mulligan population analysis was performed. The ESI-Mass spectrum analysis was performed for these quinoxaline derivatives. In this study, title molecules of DPQC and MDBD were tested for in vitro antibacterial, antioxidant, and anticancer properties which exhibited enhanced biological activities. In particular, the title molecule MDBD gave enhanced anticancer activity at the lowest concentration of 125 µg/mL against human liver cancer (HepG2) cell lines, as well as potent bactericidal activity with a maximum of (19.5 ± 1.0 mm) at 2.5 µg/mL against Yersinia enterocolitica (MTCC 840). In an (H2O2) scavenging study, MDBD revealed potent antioxidant activity (64.21%). The DPPH radical scavenging antioxidant activity of MDBD was discovered at (67.48 %) concentration at 500 µg/mL. The best binding energy between anticancer target protein, specifically c-Met-kinase (hepatocyte growth factor; PDB ID: 3F66) and DPQC and MDBD compounds, were determined using in silico molecular docking. The auto dock software provided superior results for the title compound MDBD, which exhibited a higher ligand-receptor interaction energy value of -10.8 (kcal/mol) against 3F66 protein and a 0.01187 µM inhibition constant (ki) with (active site A) presented amino acids such as A: ARG1086, A: MET1211, A: VAL1092, A: ALA1226, A: ALA1108, A: MET1211. Further, studies are warranted to explore their promising anticancer and other pharmacological and biochemical properties.

Structure analysis of ethyl ferulate from Rubus corchorifolius L.f. leaves and its inhibitory effects on HepG2 liver cancer cells

The tender leaves of Rubus corchorifolius L. f. (R. corchorifolius) have been made into herbal tea for relieving coughs in East and Southeast Asia from ancient times. Herein, we obtained an ethyl acetate extract from R. corchorifolius leaves and isolated a major bioactive compound within. Structural analysis of the isolated compound was performed by spectroscopic methods and the compound was identified as ethyl ferulate. Effect of ethyl ferulate on the growth and proliferation of human liver cancer HepG2 cells and normal human liver LO2 cells was determined by MTT assay. We found that ethyl ferulate significantly suppressed the cell proliferation of HepG2 cells (IC50 26.4 μM), while it did not cause cytotoxicity on LO2 cells. In addition, flow cytometry analysis demonstrated that ethyl ferulate inhibited HepG2 cell growth via inducing cellular apoptosis. Specifically, ethyl ferulate reduced the electrical potential of the mitochondrial membrane and increased the concentration of calcium ions inside cells. Moreover, these changes were accompanied by increases in the expression of the pro-apoptotic proteins, such as cleaved caspase-3 and Bax. In contrast, cell morphology and growth of LO2 cells remained unaffected. In conclusion, for the first time, our observations demonstrated that ethyl ferulate possesses great potential as an effective and safe antitumor agent for cancer chemoprevention in humans.

Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice.

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

Design, synthesis and anticancer activity of sulfenylated imidazo-fused heterocycles

We report herein, the design, synthesis and study of anticancer properties of sulfenylated 2-phenylimidazo[1,2-a]pyridines and their analogues. A set of twenty sulfenylated imidazo[1, 2-a]pyridine derivatives were synthesized. Whereby elusive amendments to the imidazo[1,2-a]pyridine motif confer dramatic changes in functional affinity of a novel action to modulate anticancer activity in seven different human cancer cell lines i.e.: MDA MB 231 (breast), HepG2 (liver), Hela (cervical), A549 (lung), U87MG (glioblastoma), SKMEL-28 (skin melanoma) and DU-145 (prostate) by employing MTT assay. Among the series, compounds 4e (naphthalene), 4f (styrene) and 4h (thiomethyl) showed potent activity towards human liver cancer cells HepG2. Cell cycle analysis results revealed that these compounds arrested the cell cycle at G2/M phase and induced apoptosis in human liver cancer cells HepG2. It was further confirmed by Hoechst staining, Measurement of mitochondrial membrane potential (ΔΨm) and Annexin V-FITC assay.

Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes.

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2′-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, 1H NMR, 13C NMR, UV–VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H2O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H2O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC50 values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC50 values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.

Antiproliferative effect of extracts and fractions of the root of Terminalia avicennioides (Combretaceae) Guill and Perr. on HepG2 and Vero cell lines

BackgroundTerminalia avicennioides Guill and Perr (Combretaceae) is an important West African medicinal plant. The plant is used locally against microbes and parasites in both humans and animals and studies have demonstrated its cytotoxicity potential. Thus, this study was carried out to test the cytotoxic effect of the extracts and fractions of the root of the medicinal plant Terminalia avicennioides Guill and Perr (Combretaceae) in two different cell lines.MethodsMethanol, ethanol, 30 % ethanol, hot water and cold water extracts and ethylacetate, hexane, chloroform, butanol and residual water fractions, were evaluated at 1000, 750, 500, 250, 100 and 50 µg/mL concentrations, with doxorubicin as positive control. The cells were incubated with the extracts for 48 h at 37 °C in a 5 % CO2 humidified incubator. The inhibition of cell viability, determined with the methyl blue thiazole tetrazolium bromide (MTT) assay, was used to assess the anti-proliferative effect of the extracts, in normal Vero Monkey kidney and human liver cancer (HepG2) cell lines.ResultsThere was a concentration-dependent inhibition of cell viability in both the HepG2 and Vero cell lines. For HepG2 cells, antiproliferative effect was highest for the hexane fraction (viability ranged from 19.63 ± 1.10 % to 70.30 ± 1.78 % for 1000 and 50 µg/mL, respectively. For Vero cells, the highest antiproliferative effect, at 1000 µg/mL, was with hexane fraction (cell viability 21.37 ± 3.50 %), while at 50 µg/mL the chloroform fraction demonstrated the highest effect (viability of 86.10 ± 1.95 %).ConclusionsThe extracts and fractions from the root of Terminalia avicennioides have antiproliferative effect on the Vero and HepG2 cell lines tested. However, the extracts and fractions were not more toxic to the HepG2 than to the Vero cells. The cytotoxic effect of stem-bark and leaf extracts could be evaluated in the future to determine its anticancer potential.

A new rearranged limonoid and a new benzopyran from Harrisonia perforata

• A new rearranged limonoid and a new benzopyran were isolated. • Three known limonoids and fourteen chromones were found. • Cytotoxicity evaluation against KKU-100 and HepG2 was examined. Two new compounds, a rearranged limonoid (harriforanoid) and a benzopyran (harriforanone) were isolated from the leaves and stems of Harrisonia perforata (Blanco) Merr., together with three known limonoids and fourteen known chromones. The structures of the compounds were elucidated using spectroscopic analysis. The experimental and calculated ECD spectra were used to characterize the absolute configuration of harriforanone. The cytotoxicity of each compound was assessed towards cholangiocarcinoma (KKU-100) and human liver cancer (HepG2) cell lines. However, none of these compounds exhibited any activity (IC 50 > 50 μM).

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide-Glycyrrhetinic-Acid-Based Derivatives.

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)–amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC50; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1–8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.