Human Cancer HepG2 Research Articles

In Vitro Evaluation of Cytotoxic Potential of Caladium lindenii Extracts on Human Hepatocarcinoma HepG2 and Normal HEK293T Cell Lines.

Data regarding the therapeutic potential of Caladium lindenii (C. lindenii) are insufficient. It becomes more important to explore plants as an alternative or palliative therapeutics in deadly diseases around the globe. The current study was planned to explore C. lindenii for its anticancer activity of ethanolic and hexane extracts of C. lindenii leaves against hepatic carcinoma (HepG2) and human embryonic kidney (HEK293T) cell lines. HepG2 and HEK293T cells were treated with 10, 50, 100, 200, and 400 μg/mL of ethanolic and hexane extracts of C. lindenii and were incubated for 72 h. Antiproliferative activity was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, and percentage viability were calculated through crystal violet staining and cellular morphology by Floid Cell Imaging Station. The study showed ethanolic extract exhibiting a significantly higher antiproliferative effect on HepG2 (IC50 = 31μg/mL) in a concentration-dependent manner, while HEK293T (IC50 = 241μg/mL) cells showed no toxicity. Hexane extract exhibited lower cytotoxicity (IC50 = 150μg/mL) on HepG2 cells with no effect on HEK293T (IC50 = 550μg/mL). On the other hand, the percentage viability of HepG2 cells was recorded as 78%, 67%, 50%, 37%, and 28% by ethanolic extracts, and 88%, 80%, 69%, 59%, and 50% by hexane extracts at tested concentrations of both extracts. Toxicity assay showed significantly safer ranges of percentage viabilities in normal cells (HEK293T), i.e., 95%, 90%, 88%, 76%, and 61% with ethanolic extract and 97%, 95%, 88%, 75%, and 62% with hexane extract. The assay validity revealed 100% viability in the control negative (dimethyl sulfoxide treated) and less than 45% in the control positive (cisplatin) on both HepG2 and HEK293T cells. Morphological studies showed alterations in HepG2 cells upon exposure to >50 μg/mL of ethanolic extracts and ≥400 μg/mL of hexane extracts. HEK293T on the other hand did not change its morphology against any of the extracts compared to the aggressive changes on the HepG2 cell line by both extracts and positive control (cisplatin). In conclusion, extracts of C. lindenii are proved to have significant potential for cytotoxicity-induced apoptosis in human cancer HepG2 cells and are less toxic to normal HEK293T cells. Hence C. lindenii extracts are proposed to be used against hepatocellular carcinoma (HCC) after further validations.

Sulforaphane from broccoli attenuates inflammatory hepcidin by reducing IL-6 secretion in human HepG2 cells

Cancer is a worldwide health problem, notably liver cancer. Under inflammatory conditions, pro-inflammatory cytokine can stimulate the production of hepcidin, the principal hormone for controlling iron status, leading to iron deficiency and subsequent anaemia. Sulforaphane (SF), a broccoli-derived isothiocyanate (ITC), have been indicated to inhibit the secretion of pro-inflammatory cytokines including interleukin (IL-6). Therefore, the impact of SF on IL-6 and hepcidin production in response to bacterial lipopolysaccharide (LPS) in human cancer HepG2 cells was investigated. SF suppressed LPS-induced transcription and secretion of interleukin-6 (IL-6) after 24hrs of treatment at physiologically relevant concentration (2 μM). This was associated with a decrease in hepcidin secretion. SF was not associated with any cellular toxicity, indicating the protective effect of SF against inflammatory responses including inflammatory hepcidin. This study revealed the potential usage of broccoli-derived SF as a functional food ingredient in attenuating the inflammation-induced hepatic hepcidin and reducing liver cancer risk development.

STUDY ON THE ANTIOXIDANT, ANTIBACTERIAL, AND CYTOTOXIC ACTIVITIES IN VITRO OF ROOT EXTRACTS FROM CODONOPSIS JAVANICA IN KON TUM PROVINCE, VIETNAM

Dangshen Codonopsis javanica performed high medicinal properties in herbal remedies; however, there is currently not much specific analysis for phytochemicals and bioactivities of this plant. In this study, the ethanol extract of C. javanica roots obtained from Kon Tum Province, Vietnam contained several substances as saponin, phenolic acid, terpenoid and alkaloid. The antibacterial effect of the extract showed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus cereus with the IC50 value of 150, 100, 150 and 90 μg/ml, respectively. The antioxidant capacity of the extract also displayed IC50 value of 46.8 ± 6.8 μg/ml. Moreover, the anticancer ability of the extract exhibited on two human cancer HepG2 cells (IC50 = 83.6 ± 2.7 μg/ml), and MCF-7 cells (IC50 = 95.3 ± 2.3 μg/ml). Hence, this study for the first time provide the basic data for further research of bioactivities of natural compounds Dangshen C. javanica.

Combined Effect of 60 Hz Magnetic Fields and Anticancer Drugs on Human Hepatoma HepG2 Cells

Our previous data using bacterial cells Escherichia coli have showed that 60 Hz, 50 mT magnetic fields enhance the efficacy of antibiotics. By using magnetic fields in clinical cancer chemotherapy, it is presumed to be able to enhance an anticancer drug efficacy on the target region, reduce dosage, and suppress side effects. However, since the prokaryotic bacterial cells, i.e., E.coli, differ from human cells, which are eukaryotes and multicellular organisms in many ways, it was not clear whether the magnetic fields affect an efficacy of anticancer drug against human cancer cells. In this study, we designed and produced magnetic field exposure device for human cancer cells in culture and investigated whether 60 Hz, 50 mT magnetic fields affect the efficacy of anticancer drugs against human hepatoma HepG2 cells. The results of experiments with an anticancer drug cisplatin indicated that the quantity of viable HepG2 cells become decreased significantly by the combination of cisplatin and magnetic fields, as compared to that by cisplatin alone. This suggested that 60 Hz, 50 mT magnetic fields increase the cytocidal activity of cisplatin to human hepatoma cells. The efficiency of the anticancer drugs mitomycin C and doxorubicin against HepG2 cells was also increased significantly by exposure to magnetic fields, although the time associated with the greatest enhancement of the drug's efficacy achieved by magnetic fields differed among drugs. These results suggest that 60 Hz, 50 mT magnetic fields strengthen the effect of anticancer drugs on human cancer HepG2 cells.

Synthesis, characterization, DNA binding and antitumor activities of Cu(II) complexes

A series of Cu(II) complexes of 5,5-dimethyl-2-(2-arylhydrazono)cyclohexane-1,3-dione (HLn) were synthesized by the coupling of dimedone with aniline and its derivatives. These ligands and their Cu(II) complexes were characterized by elemental analyses, IR, 1H NMR, 13C NMR, UV–Visible, X-ray diffraction analysis and magnetic measurements. Spectral studies revealed that the ligand exist in an internally hydrogen bonded keto-hydrazone form rather than the azo-enol form. The ligands (HLn) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the hydrazone moiety (NH) with deprotonation and oxygen atom of the carbonyl (CO) group. The optimized bond lengths, bond angles and quantum chemical parameters of the complexes were calculated. The calf thymus DNA binding activity of the ligands and their Cu(II) complexes were studied by absorption spectra and viscosity measurements. The antimicrobial activities of ligands and Cu(II) complexes were tested against Gram negative bacteria (Escherichia coli), Gram positive bacteria (Staphylococcus aureus) and fungal (Candida albicans). The cytotoxic activity of ligands and Cu(II) complexes was tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands and Cu(II) complexes were performed by ABTS method.

Triterpenoids and lignans from the stems of Schisandra glaucescens

Two new triterpenoids, 24(E)-3α,12α-dihydroxyl-lanost-9(11),24-dien-26-oid acid (1) and 3,4-seco-24(Z)-6α,7β-dihydroxyl-cycloart-4(28),24-dien-3,26-dioic-3-methyl ester (2), and ten known ones (3–12), together with eight lignans (13–20), were isolated from the stems of Schisandra glaucescens. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1–3, 5–7, 9, 11–13 and 15–18 were isolated from this species for the first time. 1 and 2 were evaluated for their in vitro cytotoxicities against the mouse cancer B16 cell line, human cancer HepG2 and MCF7 cell lines by MTT assay.

C18-Diterpenoid alkaloids from Delphinium anthriscifolium var. majus

Five new C18-diterpenoid alkaloids, anthriscifoltines C-G (1–5), along with four known diterpenoid alkaloids anthriscifolcines C-F (6–9), were isolated from the extract of Delphinium anthriscifolium var. majus. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). Compounds 1–5 were also evaluated for their cytotoxic activity against MCF-7, HepG2, and H460 human cancer cell lines.

Synthesis and cytotoxicity evaluation of some novel chromone annulated phosphorus heterocycles

GRAPHICAL ABSTRACT

Triterpenoids from the branch and leaf of Abies fargesii

Eighteen triterpenoids, abifarines A-R, including fourteen previously unknown and four artifacts, together with six known ones, were isolated from the branch and leaf of Abies fargesii. Their structures were elucidated by spectroscopic data analysis. The relative configurations of abifarines A and F were further confirmed by single-crystal X-ray diffraction analysis with Mo Kα irradiation. All compounds were evaluated for their in vitro cytotoxicity against the mouse cancer B16 cell line, and human cancer HepG2 and MCF7 cell lines. (24R)-cycloartane-3β,24,25-triol and (24R)-cycloartane-3β,24,25,28-tetrol showed moderate anti-proliferative effect for B16 and HepG2 cell lines with IC50 values of 32.9, 19.5 μM and 26.4, 21.5 μM, respectively.

Spectroscopic, thermal analysis and antimicrobial activities of supramolecular Cu(II) complexes

A series of Cu(II) complexes of azo dye ligands 4-(4-hydroxy-5-(aryldiazenyl)-2-thioxothiazol-3(2H)-yl)benzenesulfonamide (HLn) were synthesized by the coupling of 3-sulfamoylphenylrhodanine with aniline and its p-derivatives. These ligands and their [Cu(Ln)(CH3COO)(OH2)]H2O complexes were characterized by elemental analyses, IR, 1H NMR, UV–Visible and magnetic measurements as well as thermal analysis and X-ray diffraction. The molar conductance measurements proved that all the complexes are non-electrolytes. IR spectra showed that the ligands (HLn) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the azo group (–NN–) and oxygen atom of the deprotonated –OH group moiety, thereby forming a six-membered chelating ring and concomitant formation of an intramolecular hydrogen bond. Spectral studies revealed that the ligand exist in an internally hydrogen bonded azo-enol form rather than the keto-hydrazone form a coordinated to the metal ion in a bidentate fashion. Analytical data revealed that all the complexes exhibited 1:1 metal-ligand ratio. Based on the ESR and electronic spectral data, the bonding parameters of these complexes have been calculated. The thermodynamic parameters of the ligands (HLn) and their Cu(II) complexes are calculated using Coats–Redfern and Horowitz-Metzger methods. The antimicrobial activities of ligands were tested against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and fungal (Candida albicans). The cytotoxic activity of ligands (HLn) was tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands (HLn) were performed by ABTS method.

ChemInform Abstract: Phytosteroids and Triterpenoids with Potent Cytotoxicities from the Leaves of Chisocheton cumingianus.

AbstractSix new phytosteroids [e.g. (I)] and three new dammarane‐type triterpenoids [e.g. (II) and (III)] are isolated together with nine known triterpenoids.

Two new cembranic diterpenoids from the flowers of Nicotiana tabacum L.

Two new cembranoids, together with fifteen known ones, were isolated from the flowers of Nicotiana tabacum L. The structures of the new compounds were established as (1βH,2E,4αOH,6αOH,7E,10αH,11αH,12βOH)-10,11-epoxy-2,7-cembradiene-4,6,12-triol (1) and (1βH,2E,4αOH,6αOH,7E,10βH,11βH,12αOH)-10,11-epoxy-2,7-cembradiene-4,6, 12-triol (2) by using spectroscopic analysis, including HRESIMS, IR, one- and two-dimensional NMR. A plausible biogenetic relationship of the isolated cembranoids was proposed. The antitumor activities of selected compounds against a panel of three human cancer HepG2, A549 and HCT-116 cell lines were evaluated by the MTT assay. Compound 5 exhibited moderate activity against Hep-G2 cell lines with an IC50 value of 14.38μM.

Polymeric complexes — LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds

A series of new ligands 5-(4′-alkylphenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HLn) were synthesized from the coupling of 3-phenylamino-2-thioxothiazolidin-4-one with aniline and its p-derivatives. These ligands and their Co(II) polymeric complexes of the [(Co)2(Ln)2(HLn)(CH3COO)2(H2O)2]n have been deduced from elemental analyses, IR, 1H-NMR, X-ray diffraction and mass spectra as well as magnetic and thermal measurements. IR and 1H NMR studies reveal that the ligands (HLn) exist in the tautomeric enol/hydrazo form in both states with intramolecular hydrogen bonding. The important infrared (IR) spectral bands imply that HLn is coordinated to the metal ion in a monobasic tetradentate via NH (hydrazone), oxygen of the carbonyl group (CO), nitrogen of the NH (3-phenylamine) and thion sulfur (CS) group. The complexes are polymeric, non-electrolytes, paramagnetic and octahedral six-coordinated. The molecular and electronic structures of the investigated compounds (HLn) were also studied using quantum chemical calculations. The salmon sperm DNA (SS-DNA) binding activity of the ligands (HLn) was studied by absorption spectra. The interaction between ligands (HLn) and SS-DNA shows hypochromism effect coupled with obvious bathochromism. The values of binding constant are correlated with Hammett's constant (σR). The cytotoxic activity of ligands (HLn) and their Co(II) complexes were tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands (HLn) and their Co(II) complexes were performed by ABTS method. The antimicrobial activity of ligands HLn and their Co(II) complexes were tested against Gram negative bacteria (Escherichia coli), Gram positive bacteria (Staphylococcus aureus) and yeast (Candida albicans).

Cytotoxicity of Pure Nanodrugs of SN-38 and Podophyllotoxin Dimers in Human Cancer HepG2, KPL-4, and MCF-7 Cells

Pure nanodrugs (PNDs) is a newly designed drug materials, which is a carrier-free drug nanoparticles fabricated by the reprecipitation method. In the present study, the cytotoxicity of PNDs consisting of SN-38 dimer and podophyllotoxin dimer with size in the range 30–50 nm was evaluated in human cancer HepG2, KPL-4, and MCF-7 cells. It was observed that the cytotoxicities of PNDs were changed depending on the type of cells. In addition, PNDs coated with polysorbate 80 showed higher activity than free PNDs, which suggests that the surface state of PNDs was the one of the important factors to affect cytotoxicity.

Four cytotoxic annonaceous acetogenins from the seeds of Annona squamosa

Four new annonaceous acetogenins (ACGs), squamocin-I (1), II (2) and III (3) and squamoxinone-D (4), together with seven known ACGs (5–11), were isolated from the seeds of Annona squamosa. The structures of all isolates were elucidated and characterised by spectral and chemical methods. Compounds 1–4 were evaluated for their cytotoxicities against Hep G2, SMMC 7721, BEL 7402, BGC 803 and H460 human cancer cell lines. Compound 1 exhibited better potent activity than the positive compound and compound 3 shows selectively cytotoxical activity against H460 with IC50 values of 0.0492 μg/ml.

Stigmalactam from Orophea enterocarpa induces human cancer cell apoptosis via a mitochondrial pathway.

Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with IC50 levels of 23.0±2.67 μM and 33.2±4.54 μM, respectively, using MTT assays. At the same time the IC50 level towards murine normal fibroblast NIH3T3 cells was 24.4±6.75 μM. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.

Biotransformation of Oleaside A by Cunninghamella echinulata

AbstractBiotransformation of oleaside A (1) by Cunninghamella echinulata (ACCC 30369) was carried out to afford two products, (6R)‐6‐hydroxyoleaside A (2) and (7S)‐7‐hydroxyoleaside A (3). The structures of 2 and 3 were elucidated by extensive NMR analyses and further confirmed by single‐crystal X‐ray diffraction analysis. We also report herein the X‐ray diffraction structure of oleaside A (1) for the first time. Compounds 1–3 were evaluated for their cytotoxic activities against the A549, HCT116, HepG2, and HL‐60 human cancer cell lines.

Characterization and Antitumor Activity of a Glucan Structure-Activity Relationship Analysis

A water-soluble polysaccharide named as HPS-1 was isolated from the roots of Hedysarum polybotrys Hand.-Mazz by hot water extraction, anion-exchange and gel-permeation chromatography and tested for its antitumor activity. Its structural characteristics were investigated by FTIR, HPLC, NMR spectroscopy, GLCMS, methylation analysis, Periodate oxidation and Smith degradation. Based on the data obtained, HPS-1 was found to be an α- (14)-D-glucan, with a single α-D-glucose at the C-6 position every nine residue, on average, along the main chain. The glucan has a weight-average molecular weight of about 9.4×104 Da. MTT assay revealed that HPS-1 significantly inhibited the proliferation of Human hepatocellular carcinoma HEP-G2 cells and human gastric cancer MGC-803 cells in vitro, indicating HPS-1 could have a possible cancer therapeutic potential.

Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: A lipophilic substitute role

To alter its hydrophobicity, a series of compounds bearing 9-O-alkyl- or 9-O-terpenyl- substituted berberine were synthesized and evaluated for anticancer activity against human cancer HepG2 and HT29 cell lines. We found that the lipophilic substitute of 9-O-alkyl- and 9-O-terpenyl berberine derivatives plays a role in inhibiting the human cancer cell growth and its activity could be maximized with the optimized substitute type and chain length. Most strikingly, nonetheless, of the six compounds prepared, sample 8, a farnesyl 9-O-substituted berberine, showed either comparable or better cytotoxic activity against human cancer HepG2 cell line than that of berberine. Compound 8 had also shown a 104-fold antiproliferation activity in compare with berberine against human hepatoma HepG2 cell lines after 48 incubation hours. Further, in Hoechst 33258 and annexin V-FITC/PI staining analyses it induced apoptosis in HepG2 cells at lower concentration than that of berberine for 24h. Take all; farnesyl 9-O-substituted berberine could be a potential candidate for new anticancer drug development.

Biotransformation of arenobufagin and cinobufotalin by Alternaria alternata

The biotransformation of arenobufagin (1) and cinobufotalin (2), isolated from the natural medicine Chan Su, by Alternaria alternata AS 3.4578 was carried out. Incubation of 1 and 2 afforded six metabolites: 3-oxo-arenobufagin (1a), ψ-bufarenogin (1b), 3-oxo-ψ-bufarenogin (1c), 3-oxo-Δ4-derivative of cinobufotalin (2a), 3-oxo-cinobufotalin (2b) and 12β-hydroxycinobufotalin (2c). Among them, metabolites 1a, 1c and 2c are new compounds and their structures were characterized on the basis of their spectroscopic data (NMR, MS and IR). Compounds 1, 2, 1b, 2a and 2b were evaluated for their cytotoxicity against HepG2 and MCF-7 human cancer cells, and all of them showed significant inhibitory activities.