Human Hepatoma SMMC-7721 Cells Research Articles

Diselaginellin B, an Unusual Dimeric Molecule from Selaginella pulvinata, Inhibited Metastasis and Induced Apoptosis of SMMC-7721 Human Hepatocellular Carcinoma Cells.

Two new unusual dimeric selaginellins, diselaginellins A and B (1 and 2), along with two known derivatives, selaginellin (3) and selaginellin B (4), were isolated from Selaginella pulvinata. Their structures were elucidated by extensive NMR and high-resolution ESIMS data analysis. Compound 2 displayed apoptosis-inducing and antimetastatic activities against the human hepatocellular carcinoma cell line SMMC-7721. A microarray analysis revealed that genes related to metabolism, angiogenesis, and metastasis were altered by 2. The up- and down-regulation of the mRNA levels of related genes was confirmed by RT-qPCR. Metabolism modulation and metastasis inhibition might be the mechanisms of the antitumor properties of diselaginellin B (2).

The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa.

Polysaccharides extracted from the mushroom Grifola frondosa (GFP) are a potential anticancer agent. The objective of this study was to investigate the effect of GFP and vitamin C (VC) alone and in combination on the viability of human hepatocarcinoma SMMC-7721 and HepG2 cells. Studies designed to detect cell apoptosis and autophagy were also conducted to investigate the mechanism. Results from the cell viability assay indicated that a combination of GFP (0.2 or 0.25mg/mL) and VC (0.3mmol/L) (GFP/VC) led to 52.73 and 53.93% reduction in cell viability of SMMC-7721 and HepG2 cells separately after 24h. Flow cytometric analysis indicated that GFP/VC treatment induced cell cycle arrest at the G2/M phase, and apoptosis occurred in approximately 43.62 and 42.46% of the SMMC-7721 and HepG2 cells separately. Moreover, results of Hoechst33258 and monodansylcadaverine staining, and transmission electron microscopy, showed that GFP/VC induced apoptosis and autophagy in SMMC-7721 and HepG2 cells. Western blot analysis showed changes in the expression of apoptosis-related proteins [upregulation of BAX and caspase-3, downregulation of Bcl-2, and activation of poly-(ADP-ribose)-polymerase] and autophagy protein markers (upregulation of beclin-1 and microtubule-associated protein 1A/1B light chain-3). We also demonstrated that the expression of both Akt and p-Akt was enhanced, suggesting the PI3K/Akt/mTOR pathway might not be involved in this process. Our study shows that the combined application of GFP and VC induced cell apoptosis and autophagy in vitro, and might have antitumor activity in vivo.

Ganoderic acid A inhibits proliferation and invasion, and promotes apoptosis in human hepatocellular carcinoma cells.

Ganoderic acid A (GA-A), a triterpenoid, has been demonstrated to suppress cell proliferation in various cancers, including breast cancer and osteosarcoma. However, its effect on human hepatocellular carcinoma (HCC) remains to be elucidated. The present study aimed to investigate the effect of GA-A on HCC cells in vitro. The HepG2 and SMMC7721 human HCC cell lines were treated with differing concentrations of GA-A for 24, 48 and 72 h. The cell growth rate, cell cycle and apoptosis, migration and invasion were determined using a Cell Counting Kit-8, flow cytometry and transwell assays, respectively. The expression of apoptosis-associated proteins was detected via western blot analysis. GA-A significantly inhibited the proliferation of human HCC HepG2 and SMMC7721 cells in a dose-dependent manner. Furthermore, GA-A induced cell cycle arrest at the G0/G1 phase and apoptosis, and suppressed the migration and invasion of HCC cells. Furthermore, GA-A decreased the expression of cyclin D1 and increased the expression of p21 and cleaved caspase-3. In conclusion, GA-A suppressed the proliferation of human HCC cells in vitro and may act as a promising natural therapeutic reagent in the treatment of HCC.

The role of Jagged1/Notch pathway-mediated angiogenesis of hepatocarcinoma cells in vitro, and the effects of the spleen-invigorating and blood stasis-removing recipe.

The objective of this study was to observe the effect of Jagged1/Notch pathway-mediated angiogenesis on the in vitro proliferation of hepatocellular carcinoma cells, and the effect and possible mechanism of the spleen-invigorating and blood stasis-removing recipe. Spleen-invigorating and blood stasis-removing recipe serum from SPF grade nude mice was prepared, and the fingerprint of the drugs of the spleen-invigorating and blood stasis-removing recipe and drug serum were identified by HPLC. SMMC-7721 human hepatocellular carcinoma cells were divided into the normal control group, DAPT inhibitor control group, and drug serum group according to the different treatments. The Cell Counting Kit-8 (CCK-8) method was used to determine cell proliferation ability, and angiogenesis was observed under an inverted microscope. The expression of Jagged1, Notch1, and VEGF was measured by qPCR and western blot analysis. The interaction of Jagged1 and Notch1 was detected by Co-IP. The CCK-8 assay indicated that cell proliferation was inhibited in response to drug treatment (P<0.01). The expression of Jagged1, Notch1, and VEGF in the drug serum group was significantly lower than in the normal control group (P<0.01). Compared with the control group, the new vascular area of the DAPT inhibitor control group and drug serum group was smaller, and the blood vessels of the DAPT inhibitor control group and drug serum group were more sparse. The levels of Jagged1, Notch1, VEGF protein and the interaction between Jagged1 and Notch1 in the DAPT inhibitor control group and drug serum group were significantly lower than in the control serum group (P<0.01). In conclusion, the spleen-invigorating and blood stasis-removing recipe can inhibit the proliferation of hepatocellular carcinoma cells, and tumor angiogenesis in vitro. The function is related to the reduced expression of Jagged1, reduced interaction between Jagged1 and Notch1, and the reduced expression and activity of VEGF.

Isolation of three cyanins from Lonicera caerulea L. fruits and its anticancer activity

Lonicera caerulea L. fruit is an excellent source of bioactive compounds. An efficient separation method of cyanins is important for the development of many value-added products and functional food ingredients. High-speed counter-current chromatography (HSCCC) was applied to isolate cyanins from Lonicera caerulea fruits with a biphasic solvent system composed of methyl tert-butyl ether/n-butanol/acetonitrile/water/trifluoroacetic acid (2:2:1:5:0.01, volume ratio). 1.41 mg of cyanidin 3, 5-O-diglucoside, 1.08 mg of cyanidin 3-O-rutinoside and 6.38 mg of cyanidin 3-O-glucoside were obtained from 40 mg of crude extract. The purities of these compounds were 95.8%, 92.4% and 97.6%, respectively, as identified by high-performance liquid chromatography–diode array detection (HPLC-DAD) and high-performance liquid chromatography-electrospray ionization mass spectrometryn (HPLC-ESI/MSn). In addition, the dominant anthocyanin, cyanidin 3-O-glucoside was demonstrated cytotoxic response of human hepatocarcinoma SMMC-7721 cells, inducing live cancer cell apoptotic by flow cytometric analysis.

Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation

Our previous study revealed that insufficient radiofrequency ablation (RFA) promotes the malignancy of human hepatocellular carcinoma (HCC) SMMC7721 cells via the Ca2+/calmodulin-dependent protein kinase II (CaMKII)/extracellular signal-regulated kinase (ERK)-induced overexpression of vascular endothelial growth factor (VEGF). The aims of the present study were to address the involvement of epidermal growth factor receptor (EGFR) transactivation in the enhanced SMMC7721 cell proliferation induced by insufficient RFA, in addition to its association with the CaMKII/ERK/VEGF signaling cascade. SMMC7721 cells were subjected to a 47°C treatment regimen to simulate insufficient RFA. Cell proliferation was determined using MTT and colony formation assays. The expression levels of VEGF, CaMKII, phosphorylated (phospho)-CaMKII, ERK, phospho-ERK, EGFR and phospho-EGFR were analyzed using western blotting. The results demonstrated that the enhancement of SMMC7721 cell proliferation by the 47°C treatment regimen was significantly inhibited by exposure of the cells to AG178 (a specific inhibitor of EGFR). Furthermore, AG1478 exposure prevented the overexpression of VEGF and phosphorylation of ERK, but had no significant effects on CaMKII phosphorylation. By contrast, 47°C treatment-induced EGFR phosphorylation was inhibited by treatment with KN93 (a specific inhibitor of CaMKII). Overall, the results of the present study have suggested a role for EGFR transactivation in the RFA-promoted growth of residual HCC. Thus, targeting EGFR may represent a useful preventive and therapeutic strategy for RFA-induced HCC progression and recurrence.

Suppression of the Wnt signaling pathway may contribute to the inhibition of proliferation of human hepatocellular carcinoma SMMC-7721 cells by esculetin.

The aims of the present study were to investigate the effects of esculetin on the proliferation of human hepatocellular carcinoma SMMC-7721 cells and to determine the underlying mechanism behind this activity. An MTT assay was used to assess cell proliferation, reverse transcription-quantitative polymerase chain reaction was used to determine the relative mRNA expression levels of β-catenin, c-Myc and cyclin D1, and western blot analysis was utilized to determine the levels of the associated proteins. Compared with the dimethyl sulfoxide control, esculetin reduced the cell viability of SMMC-7721 and HL-7702 cells in a dose- and time-dependent manner. Treatment of SMMC-7721 cells with esculetin resulted in downregulation of the mRNA and protein levels of β-catenin, c-Myc and cyclin D1. Esculetin increased the phosphorylation of β-catenin at Ser33/Ser37/Thr41 and inhibited the proliferation of human hepatoma SMMC-7721 cells by suppressing the Wnt signaling pathway. The results of the present study suggest that esculetin inhibited the Wnt/β-catenin signaling pathway in SMMC-7721 cells and may have potential as an effective anti-cancer drug, acting to inhibit the Wnt/β-catenin signaling pathway.

The effects of propofol on the growth behavior of hepatoma xenografts in Balb/c mice

ObjectiveStudies on the effects of propofol on the growth of hepatoma xenografts in Balb/c mice. MethodsIn an effort to establish a hepatoma-xenograft model of BALB/C mice, human hepatocellular carcinoma cells SMMC-7721 were inoculated subcutaneously into BALB/C mice. Forty mice were randomly divided into five different groups (n=8): control group (C group), Intralipid group (Y group), low dose (50mg/kg) propofol group (P1 group), medium dose (100mg/kg) propofol group (P2 group) and high dose (150mg/kg) propofol group (P3 group). The tumor volume was measured before treatment and every 3days after treatment (T0d-T18d, T0 represents time point before treatment, T3d-T18d represent time points every 3days after treatment for a total of 18 days). All mice were sacrificed 19days after drug withdrawal. The tumor masses were extracted, weighed, and the tumor inhibition rate of propofol was calculated. The protein levels of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the xenografted tumors were analyzed by immunohistochemistry staining. ResultsNo statistical significance in the tumor volume at T0d (before treatment), T3d (3days after treatment), and T6d (6days after treatment) among the five groups (P>0.05) could be determined. Compared to group C, the tumor volumes in the P1, P2, and P3 groups were found to be significantly decreased in size upon increasing the propofol dosages (P<0.05). There was no statistical significance at time points T9d-T18d in group Y compared to group C (P>0.05). The tumor weights in the P1, P2, and P3 groups were found to be significantly lower as the propofol dosages increased (P<0.05), with no statistical significance determined in group Y (P>0.05). MMP-2 and VEGF protein levels were found to be significantly lower in the P1, P2, and P3 groups as the propofol dosages increased (P<0.05), with no statistical significance in group Y (P>0.05). ConclusionWithin a certain range, propofol was found to inhibit tumor growth and expression of MMP-2 and VEGF proteins in hepatoma xenografts in BALB/C mice in a dose-dependent manner.

Role of the cystathionine β-synthase/H2S system in liver cancer cells and the inhibitory effect of quinolone-indolone conjugate QIC2 on the system.

Hydrogen sulfide(H2S), the third gasotransmitter, plays important roles in cancer biological processes. As endogenous H2S exerts pro-cancer functions, inhibition of its production in cancer cells may provide a new cancer treatment strategy and be achieved via regulation of the function of cystathionineβ-synthase (CBS), one of the main metabolic enzymes synthesizing H2S. This enzyme plays important roles in the development and progression of colon and ovarian cancer, primarily regulating mitochondrial bioenergetics and accelerating cell cycle progression. In the present study, we firstly investigated the role of the CBS/H2S system in human hepatoma cells, and then the inhibitory effect of a quinolone-indolone conjugate QIC2 on this system. When CBS was overexpressed in human hepatoma HepG2 and SMMC-7721 cells, inhibition of endogenous CBS/H2S significantly reduced their viability and growth rate, as well as the proliferation of SMMC-7721 cells. Meanwhile, CBS knockdown caused multiple effects, including apoptosis of SMMC-7721 cells, an increase in the Bcl-2-associatedX protein (Bax)/Bcell lymphoma/leukemia (Bcl-2) ratio, activation of caspase-3 and polyADP-ribose polymerase (PARP), when compared with the scramble siRNA (ScsiRNA)-transfected groups. Heme oxygenase-1 (HO-1; a microsomal enzyme) expression was significantly decreased while the reactive oxygen species (ROS) level was increased in the CBS siRNA-transfected SMMC-7721 cells. QIC2 significantly reduced SMMC-7721 cell viability in a dose-dependent manner and showed a lower toxicity in human normal liver HL-7702 cells relative to the positive controls sunitinib and doxorubicin (DOX). The compound also inhibited cell proliferation and induced cell apoptosis in SMMC-7721 cells. Further analysis indicated that QIC2 downregulated the CBS/H2S system, decreased both HO-1 protein and glutathione (GSH) levels while increased the ROS level and activated the caspase-3 cascade. Collectively, our results demonstrated that the CBS/H2S system plays important roles in human hepatoma cells and QIC2 significantly inhibited cell growth via downregulation of the system.

Cytotoxic Fusicoccane-Type Diterpenoids from Streptomyces violascens Isolated from Ailuropoda melanoleuca Feces.

Six new fusicoccane-type diterpenoids (2-7) were isolated from the fermentation broth of Streptomyces violascens, which was isolated from Ailuropoda melanoleuca (giant panda) feces. The structures of these new compounds were elucidated by a detailed spectroscopic data and X-ray crystallographic analysis. Compounds 5-7 demonstrated cytotoxicity against five human cancer cell lines, with IC50 values ranging from 3.5 ± 0.7 to 14.1 ± 0.8 μM. Cell adhesion, migration, and invasion assays showed that 6 inhibited the migration and invasion of human hepatocellular carcinoma SMMC7721 cells in a dose-dependent manner. Through further investigation, it was revealed that 6 inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in addition to down-regulating the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels to influence the migration and invasion of cancer cells.

Esculetin induces apoptosis of SMMC-7721 cells through IGF-1/PI3K/Akt-mediated mitochondrial pathways.

Esculetin (6,7-dihydroxycoumarin) is a coumarin derivative extracted from natural plants and has been reported to have anticancer activity. However, the mechanism by which esculetin prevents human hepatic cancer cell growth is still largely unknown. In this study, we investigated the effect of esculetin on human hepatocellular carcinoma (HCC) SMMC-7721 cells and explored the cell signal mechanism. Our data indicated that esculetin induced apoptosis in SMMC-7721 cells, which were supported by DAPI staining and Annexin V/PI staining. Meanwhile, esculetin increased the activities of caspase-3 and caspase-9, promoted bax expression, decreased bcl-2 expression, and triggered collapse of mitochondrial membrane potential, and increased cytochrome c release from mitochondria. In addition, the inactivation of IGF-1, PI3K, and Akt was observed after esculetin administration. Furthermore, pretreatment with IGF-1 before esculetin administration abrogated the pro-apoptotic effects of esculetin, while PI3K inhibitor increased the pro-apoptotic effects of esculetin. These results indicated that esculetin induced the apoptosis of SMMC-7721 cells through IGF-1/PI3K/Akt-regulated mitochondrial dysfunction.

MiR-124 inhibits the migration and invasion of human hepatocellular carcinoma cells by suppressing integrin \u03b1V expression

Tumor metastasis is the major cause of cancer-related death especially in human hepatocellular carcinoma (HCC). Although microRNAs have been implicated in tumor development, the roles of miR-124 in HCC metastasis are still not well understood. We conducted functional analysis in this study to investigate miR-124. We observed that miR-124 significantly retarded the wound healing and migration of HCC SMMC-7721 and BEL-7404 cells. Further analysis indicated miR-124 directly targeting the transcriptional factor Sp1 which is an important transcription factor for the integrin αV subunit gene transcription. Co-transfection of miR-124 with the luciferase reporter containing Sp1 3′ untranslated region (UTR) significantly suppressed the luciferase activities. While mutation of the binding site of miR-124 in Sp1 mRNA 3′UTR completely abrogated the suppression of miR-124. Overexpression of miR-124 resulted in robust downregulation of Sp1 and integrin αV expression at either mRNA or protein level. Ectopic expression of miR-124 in HCC dramatically repressed the wound healing and migration in vitro and tumor metastasis in mouse experiments. Our findings demonstrated that miR-124 played as an important role in regulation of integrin αV expression in HCC, and reintroduction of miR-124 might be an alternative therapeutic strategy for controlling integrin αV expression in HCC.

Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway.

AIMTo explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway.METHODSThe experiments were conducted on three groups: an experimental group (with ST ethanol extracts’ concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes.RESULTSCompared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased (P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased (P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.CONCLUSIONST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway.

Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome.

This study compared the sensitivity of human hepatoma Hep3B, SK-HEP-1, SMMC-7721, and BEL-7402 cells to cardiac steroids, including bufalin (BF), a bufalin derivative (BF211), ouabain (OUA), and digitoxin (DIG). Hep3B cells exhibited relatively low sensitivity to cardiac steroids. Expression levels of subunits of Na+/K+-ATPase were high in Hep3B cells. However, colocalization of Na+/K+-ATPase and caveolin was nearly undetectable in Hep3B cells. By using RNA-Seq technology, we found a total of 36 genes to be differentially expressed between Hep3B cells and SK-HEP-1 cells, which are highly sensitive to cardiac steroids. Our bioinformatics analysis determined that these genes were mostly comprised of extracellular space, protein binding, and extracellular region. Among these 36 genes, apolipoprotein E (APOE) played a critical role, as knockdown APOE expression induced colocalization of Na+/K+-ATPase and caveolin and increased sensitivity of Hep3B cells to both proliferation-inhibiting and cytotoxic effects of BF or BF211. Also, the effects of BF on PI3K/AKT/GSK3β and apoptosis signal cascades were enhanced in APOE knockdown cells. The results of our study confirmed the role of Na+/K+-ATPase signalosome in cytotoxicity of cardiac steroids and suggested that APOE regulated the sensitivity of cells to cardiac steroids by affecting formation and function of Na+/K+-ATPase signalosome. In addition, intercellular interaction with high level of Na+/K+-ATPase β1 subunit may be also a factor in the low sensitivity of Hep3B cells to cardiac steroids. Mol Cancer Ther; 15(12); 2955-65. ©2016 AACR.

A Novel Method to Synthesize 4-Aryl-1H-1,2,3-Triazoles and its Antihepatoma Activity.

A novel synthetic method of 4-substituted aryl-1H-1,2,3-triazoles from arylglyoxaldoxime semicarbazone with sodium dithionite and O2 was found to be safer than the Huisgen azide- alkyne dipolar cycloaddition. A total of 17 new structures of 4-substituted aryl-1H-1,2,3- triazoles were characterized by 1H NMR, 13C NMR, ESI-MS. Subsequently, their in vitro antihepatoma activities were evaluated on human hepatoma QGY-7703, Bel-7402 and SMMC-7721 cell lines and mouse fibroblast cells L-929 by MTS assay. Among them, 5k exhibited excellent activity against QGY-7703 (GI50 = 0.0232 μM), while 5p and 5q displayed good activity (GI50 = 0.103 μM and GI50 = 0.182 μM) against the growth of SMMC-7721 cell lines. Furthermore, 5k, 5p and 5q showed slight selectivity of inhibition on hepatoma cell lines over normal cell line L-929.

Redox responsive liposomal nanohybrid cerasomes for intracellular drug delivery

Cerasome is a freshly developped bilayer vehicle that resemble traditional liposome but has higher mophorlogical stability. In this study, a novel redox-responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method. RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes. In addition, in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile: accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in the presence of 10mM of GSH. Under the same condition, the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results. RRC showed non-toxic to human embryonic kidney 293 cells, indicating that this material has good biocompatibility. On the other hand, DOX/RRCs showed a resemble IC50 (half inhibitory concentration) value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells. IC50 values at 48h were found to decrease in the following order: DOX/RIC>DOX/RRC>DOX. Taken together, the RRC developped in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery.

Biosynthesis of Silver Nanoparticles Using Taxus yunnanensis Callus and Their Antibacterial Activity and Cytotoxicity in Human Cancer Cells.

Plant constituents could act as chelating/reducing or capping agents for synthesis of silver nanoparticles (AgNPs). The green synthesis of AgNPs has been considered as an environmental friendly and cost-effective alternative to other fabrication methods. The present work described the biosynthesis of AgNPs using callus extracts from Taxus yunnanensis and evaluated their antibacterial activities in vitro and potential cytotoxicity in cancer cells. Callus extracts were able to reduce silver nitrate at 1 mM in 10 min. Transmission electron microscope (TEM) indicated the synthesized AgNPs were spherical with the size range from 6.4 to 27.2 nm. X-ray diffraction (XRD) confirmed the AgNPs were in the form of nanocrystals. Fourier transform infrared spectroscopy (FTIR) suggested phytochemicals in callus extracts were possible reducing and capping agents. The AgNPs exhibited effective inhibitory activity against all tested human pathogen bacteria and the inhibition against Gram-positive bacteria was stronger than that of Gram-negative bacteria. Furthermore, they exhibited stronger cytotoxic activity against human hepatoma SMMC-7721 cells and induced noticeable apoptosis in SMMC-7721 cells, but showed lower cytotoxic against normal human liver cells (HL-7702). Our results suggested that biosynthesized AgNPs could be an alternative measure in the field of antibacterial and anticancer therapeutics.

Induction of Apoptosis in Human Hepatoma SMMC-7721 Cells by Polysaccharides from &lt;em&gt;Lycium barbarum&lt;/em&gt; L.

Induction of Apoptosis in Human Hepatoma SMMC-7721 Cells by Polysaccharides from &lt;em&gt;Lycium barbarum&lt;/em&gt; L.

Effects of &lt;em&gt;Lycium barbarum&lt;/em&gt; Polysaccharides on the Apoptosis of Human Hepatoma SMMC-7721 Cells

<em>Lycium barbarum</em> polysaccharide is a natural functional component which has a variety of biological activities. The composition and apoptosis inducing activities on human hepatoma SMMC-7721 cells of <em>Lycium barbarum</em> Polysaccharide fraction (LBP1) was investigated. The results showed that LBP1 consisted of neutral sugars, uronic acid and protein. LBP1 was composed of three kinds of monosaccharides including mannose, galactose and glucose. The molecule weight of LBP1 was 367 KDa. SMMC-7721 cells were cultured in the presence of LBP1 at various concentrations (50-400 mg/L) for 2 days, 4 days and 6 days and the percentage of cell viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. We found that anti-proliferative effect of LBP1 was associated with apoptosis on SMMC-7721 cells by morphological changes and cell cycle arresting at G0/G1phase. Furthermore, LBP1 could induce cell apoptosis which was closely accompanied with the enhancement of Reactive Oxygen Species (ROS) level, dissipation of Mitochondria Membrane Potential (MMP), increase expression of Bax mRNA and decrease expression of Bcl-2 mRNA. These results suggested that SMMC-7721 cell apoptosis induced by LBP1 mainly was mediated by mitochondrial pathways. However, further research on the molecular mechanisms of LBP1 effecting on the cells’ mitochondria is necessary.

Trivalent chromium alleviates oleic acid induced steatosisin SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis.

Trivalent chromium [Cr(III)] has been shown as an essential trace element for human health. Previous studies depict that Cr(III) plays important roles in maintaining normal glucose and lipid metabolism, whereas its effect on the hepatic lipid metabolism is still unknown. In the present study, we investigated the effects and underlying mechanisms of Cr on hepatic steatosis induced by oleic acid (OA) in human hepatoma SMMC-7721 cells. Hepatic steatosis model was co-administered with Cr. Indexes of lipid accumulation were determined and associated genes expression were analyzed. The data showed that OA could induce lipid accumulation and triglyceride (TG) content in SMMC-7721 cells, and significantly increase the expression of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). This steatosis effect of OA was ameliorated by Cr. The TG accumulation and up-regulation of CD36 and DGAT2 genes followed steatosis induction were inhibited by Cr. After the treatment of Cr, excessive intracellular OA content was also attenuated. Furthermore, Cr still performed inhibitory effect of DGAT2 expression at the presence of DGAT2 agonist or inhibitor, which indicated that the inhibitory effect of Cr on lipogenesis is associated with the downregulation of DGAT2 expression. These findings demonstrate that Cr alleviates hepatic steatosis via suppressing CD36 expression to prevent fatty acid uptake, as well as suppressing DGAT2 expression to inhibit TG synthesis. It suggests that CD36 and DGAT2 might become the novel drug targets for their properties in hepatic steatosis. Most importantly, Cr may be a potential anti-steatosis candidate to offer protective effects against liver damage.