Human Liver HepG2 Cancer Cell Research Articles

Antiproliferative Effect of 7-Ketositosterol in Breast and Liver Cancer Cells: Possible Impact on Ceramide, Extracellular Signal-Regulated Kinases, and Nuclear Factor Kappa B Signaling Pathways

Background: This study aimed to examine the effect of 7-Ketositosterol (7-KSS), on sphingomyelin/ceramide metabolites and apoptosis in human breast MCF-7 and human liver HepG2 cancer cells. Methods: Anti-proliferative effects of 7-KSS treatment were assessed at different concentrations and periods. Cell viability was assessed through MTT analysis, whereas the levels of sphingosine-1-phosphate (S1P), sphingomyelins (SMs), and ceramides (CERs) were measured using LC-MS/MS. Phosphorylated 44/42 ERK1/2 and NF-κB p65 (Ser536) protein levels were measured by Western blot analysis and immunofluorescence staining. Apoptosis was evaluated by TUNEL staining and flow cytometric assessment of annexin-V and propidium iodide (PI) labeling. Results: Treatment with 7-KSS significantly decreased cell survival and S1P, p-44/42 ERK1/2, and p-NF-κB p65 protein levels in cancer cells compared to controls. A substantial rise was detected in intracellular amounts of C16-C24 CERs and apoptosis in cancer cells incubated with 7-KSS. Conclusions: 7-KSS stimulated ceramide accumulation and apoptosis while decreasing cell proliferation via downregulating S1P, p-44/42 ERK1/2, and p-NF-κB p65 protein levels.

Synthesis, biological activity, and in silico studies of thieno[2,3-d]pyrimidine and thieno[2,3-d]triazine derivatives

Background The chemistry of condensed heterocyclic compounds has emerged in numerous reports for their diverse biological properties and drug discovery. Pyrimidine and triazine scaffolds have been utilized as therapeutic agents in many medicinal applications. Many research groups have designed and synthesized pyrimidine moieties as they are incorporated in nucleic acid bases.Objective In this report, we have designed and synthesized a variety of 2-mercaptothieno pyrimidine and thienotriazine derivatives and 2-mercaptothienopyrimidines conjugated with sugar moiety. The newly synthesized compounds were tested for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as a normal cell line (human normal melanocyte, HFB4) and were also analyzed for in silico studies to determine their potential.Materials and methods A variety of 2-mercaptothienopyrimidine and thienotriazine derivatives were prepared via cyclization of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) and 2-amino-N-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9). Two derivatives of 2-mercaptothienopyrimidines conjugated with sugar moiety were also prepared. The products were screened for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison with the known anticancer drug 5-fluorouracil using the MTT assay.Results and conclusion The results indicated that most of the tested compounds exhibited no activity against the growth of HFB4. Compounds 5, 8, 10, 12, and 14 revealed effective antiproliferative activity against MCF-7 cell lines with IC50 of 4.6, 6.2, 5.4, 7, and 3.25 µg/ml, respectively, compared with 5-fluorouracil (IC50 of 3.97 µg/ml). In the same sense, the evaluation of cytotoxic effect of the tested compounds against human liver HepG-2 cancer cell lines revealed that compounds 5, 8, 10, 12, and 14 showed cytotoxic activity close to that of the standard drug (IC50 values of 5.77±0.99, 7.23±0.98, 4.42±1.32, 7.9±0.90, and 5.1±11.28 µg/ml, respectively, vs. 4.27±0.58 µg/ml for 5-fluorouracil). Free binding energy was estimated by docking and MM-GBSA calculation. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the cytotoxic effect. Compound 14 illustrated the highest MM-GBSA value (−20.38) and the best cytotoxic effect.

Dipteran Carboxymethyl Chitosan as an Inexhaustible Derivative with a Potential Antiproliferative Activity in Hepatocellular Carcinoma Cells.

Traditional folk therapies indicate that insects have diverse medicinal potentials. However, the therapeutic application of insect chitosan and its derivatives has not been explored. To investigate the application of chitosan and its derivatives, the carboxymethyl derivative of chitosan (CM-Ch) was extracted from two dipteran larvae species, Chrysomya albiceps and Sarcophaga aegyptiaca. The degree of deacetylation (DD) and CM-Ch functional groups were validated using Fourier-transform infrared (FTIR) spectroscopy analysis and proton nuclear magnetic resonance spectroscopy (1H NMR), respectively. The molecular weight was estimated using MALDI-TOF MS analysis. The effect of CM-Ch on the morphology and proliferation of human liver HepG2 cancer cells was assessed. IC50 of CM-Ch induced significant growth-inhibitory effects in HepG2 cells. CM-Ch treatment altered the morphology of HepG2 in a dose-dependent manner and induced apoptosis in a caspase-dependent manner. CM-Ch treatment showed no signs of toxicity, and no alterations in liver and kidney biochemical markers were observed in albino rats. A CM-Ch derivative from commercial crustacean chitosan was used to assess the efficacy of the insect-derived CM-Ch. The data presented here introduce insect CM-Ch as a promising, inexhaustible, safe derivative of chitosan with antitumor potential in liver cancer. This is the first report highlighting the anticancer activity of insect CM-Ch in hepatocellular carcinoma cells.

Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways

In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 μg.mL−1) was found to be significantly more potent than CME (IC50: 87.5 μg.mL−1) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.