scholarly journals Caspase Mediated Synergistic Effect ofBoswellia serrataExtract in Combination with Doxorubicin against Human Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Ahmed Khan ◽  
Mhaveer Singh ◽  
Masood Shah Khan ◽  
Abul Kalam Najmi ◽  
Sayeed Ahmad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Cell Lines ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Hepatic Toxicity ◽  
Isobolographic Analysis ◽  
Ic50 Value ◽  
Hep3b Cells ◽  
Synergistic Behavior

The study investigated the growth-inhibiting and apoptosis mediating effects ofB. serrataextract as monotherapy and combination therapy with DOX against hepatocellular carcinoma cell lines. Boswellic acid rich fraction ofB. serrataextract was prepared. MTT assay on HepG2 and Hep3B cells was carried out usingB. serrataalone and in combination with DOX. Further, caspase-3 activity, TNF-αlevel, and IL-6 level were estimated. Isobolographic analysis was carried out to evaluate the effect of combination therapy. Additionally, protective effect ofB. serrataextract on DOX induced hepatic toxicity was also evaluated in Wistar rats.B. serrataextract inhibited growth of HepG2 (IC50 value of21.21±0.92 μg/mL) as well as HepG2 (IC50 value of18.65±0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of1.06±0.04 μg/mL and1.92±0.09 μg/mL. Isobolographic analysis showed combination index (CI) of DOX andB. serrataextract of0.53±0.03to0.79±0.02suggesting synergistic behavior against the two cell lines.B. serrataextract also caused dose dependent increase in caspase-3 activity, TNF-αlevel, and IL-6 level which was higher (P<0.001) with DOX (1 μM) andB. serrataextract (20 μg/mL) combination.B. serrataextract also protected Wistar rats against DOX induced hepatic toxicity.

scholarly journals Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1878 ◽  
Author(s):  
Sami Znati ◽  
Rebecca Carter ◽  
Marcos Vasquez ◽  
Adam Westhorpe ◽  
Hassan Shahbakhti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Cell Lines ◽  
Radiation Treatment ◽  
Combined Treatment ◽  
New Combination ◽  
Migration And Invasion ◽  
Syngeneic Mouse Model

Hepatocellular Carcinoma (HCC) is increasing in incidence worldwide and requires new approaches to therapy. The combination of anti-angiogenic drug therapy and radiotherapy is one promising new approach. The anti-angiogenic drug vandetanib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and RET proto-oncogene with radio-enhancement potential. To explore the benefit of combined vandetanib and radiotherapy treatment for HCC, we studied outcomes following combined treatment in pre-clinical models. Methods: Vandetanib and radiation treatment were combined in HCC cell lines grown in vitro and in vivo. In addition to 2D migration and clonogenic assays, the combination was studied in 3D spheroids and a syngeneic mouse model of HCC. Results: Vandetanib IC 50 s were measured in 20 cell lines and the drug was found to significantly enhance radiation cell kill and to inhibit both cell migration and invasion in vitro. In vivo, combination therapy significantly reduced cancer growth and improved overall survival, an effect that persisted for the duration of vandetanib treatment. Conclusion: In 2D and 3D studies in vitro and in a syngeneic model in vivo, the combination of vandetanib plus radiotherapy was more efficacious than either treatment alone. This new combination therapy for HCC merits evaluation in clinical trials.

scholarly journals ID: 1085 Sodium citrate induces apoptosis in HepG2 cell lines

2017 ◽  
Vol 4 (S) ◽  
pp. 174
Author(s):  
Sinh Truong Nguyen ◽  
Phuc Hong Vo ◽  
Oanh Thi-Kieu Nguyen ◽  
Nghia Minh Do ◽  
Phuc Van Pham
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Dna Fragmentation ◽  
Hepg2 Cell ◽  
Cell Lines ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Sodium Citrate ◽  
Dependent Manner ◽  
Hepg2 Cell Lines

PURPOSES: Cancer cells were observed to increase glucose uptake and fermentation of glucose to lactate to to synthesis rapidly ATP for cell growth, survival and proliferation. Thus, inhibition of glycolysis might be useful in antitumor treatment. This phenomenon occurred even with fully functioning mitochondria, and known as Warberg effect. Sodium citrate, an inhibitor of Warberg effect, was reported to antiproliferate many cancer cells line. However, sodium citrate has not been studied in Hepatocellular Carcinoma cells line yet. Here we aimed to investigate the effect of sodium citrate in HepG2 cells line.   MATERIAL AND METHODS: HepG2 cell lines was treated with sodium citrate at different concentrations. Viable cells were determined by Alamar Blue. The apoptosis induced-cells was detected by Annexin V with FCM technique. Disintegrated nuclei and DNA fragmentation was analyzed. The activity of caspase-3 was also tested.   RESULTS: We observed that the IC50 value of sodium citrate on HepG2 is at 10mM. FCM analysis showed that sodium citrate induced apoptosis in HepG2 cell line in dose-dependent manner. At 10mM sodium citrate, the caspase-3/7 was observed to be activated in time-dependent manner. Sodium citrate also induced nuclei disintergated in HepG2. DNA fragmentation was observed when HepG2 cells were treated with 10mM sodium citrate.   CONCLUSIONS: We have shown that sodium citrate possesses the antiproliferative ability on HepG2 at IC50 10mM. Sodidum citrate induces apoptosis cells in hepatocellular carcinoma HepG2 by capases-3 activation. More investigation of glycolysis inhibition of sodium citrate on HepG2 should be performed in animals

scholarly journals ID2009 H. Odorata methanol extract inhibits hepatocellular carcinoma HepG2 cells line via induction of caspase-dependent apoptosis

2017 ◽  
Vol 4 (S) ◽  
pp. 42
Author(s):  
Sinh Truong Nguyen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Cancer Cell ◽  
Plant Extract ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Fluorescent Microscope ◽  
Ic50 Value ◽  
Hopea Odorata

Background: Globally cancer is a disease which is major burden to human health nowadays. The demand for new therapies to treat and to prevent cancer disease frequently exists. Since the toxic side effect of current treatment such as chemotherapy, the research interest is paying attention toward naturally derived-compounds because of their selective toxicity to cancer cell. This study aims to test the anticancer activity of a crude extract of Hopea odorata on HepG2 cancer cell line.   Method: Methanol extract were prepared from the bark of H. odorata plant. In vitro cytotoxicity Hopea odorata extract on human hepatocellular carcinoma cell line HepG2, compared to normal human cell fibroblast (HF), was investigated by Alamar Blue assay. Caspase-3/7 was detected using the reagent that consists of DEVD peptide conjugated to a nucleic acid-binding dye.  The apoptosis induction of plant extract on HepG2 was recognized by Annexin V/7AAD using flow cytometry. Disintergrated nuclei of plant-treated cell was observed under fluorescent microscope using Hoechst/PI staining. With the same technique of staining, the ratio of dead/total cells was determined by distingusing Hoechst and PI fluorescent signal.   Results. We found that the IC50 value of Hopea odorata extract on HepG2 is at 12.67± 5µg/ml, this value is at 44.2± 3µg/ml on HF. Vice versa, the IC50 value of Doxo on HepG2 153.3±15ng/ml while that is 6.3 ±0.6083ng/ml on HF. The selectivity index of H. Odorata extract (SI) toward HepG2 cells is approximately 3.48, while the SI of Doxorubicin toward HepG2 cells is approximately 0.04. The ratio of dead/total cells increased in dose-dependent manner when observed under fluorescent microscope, while the ratio of dead/total cells barely changed on HF cells. The plant extract inhibited HepG2 through the activation of caspase-3/7. At the concentration 250µg/ml of plant extract, 35% HepG2 cells was induced into apoptosis, and HepG2 cells appeared with disintegrated nuclei under fluorescent microscope.  Conclusion. These finding showed methanolic extract of Hopea odorata plant induced apoptosis and selectively cytotoxic toward HepG2 rather than human fibroblast cells. Purification of compounds from Hopea odorata extract need to be performed for further research the anticancer properties of Hopea odorata.

scholarly journals Anticancer effects of dihydromyricetin on the proliferation, migration, apoptosis and in vivo tumorigenicity of human hepatocellular carcinoma Hep3B cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lianggui Jiang ◽  
Wen-Chu Ye ◽  
Zuobiao Li ◽  
Yongguang Yang ◽  
Wei Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Public Health Problem ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Anticancer Effect ◽  
Caspase 9 ◽  
Hep3b Cells

Abstract Background Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anticancer effect on a variety of malignancies, but its anticancer function of DHM in HCC has been unclear. The aim of this study was designed to investigate the anticancer effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. Methods Cultured Hep3B cells were treated with different DHM concentrations, followed by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of BCL-2, Cleaved-caspase 3, Cleaved-caspase 9, BAK, BAX and BAD were validated by western blot. Results DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC cancers compared to the weights in control and NDP group. Conclusions DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

scholarly journals The Pivotal Role of Long Noncoding RNA RAB5IF in the Proliferation of Hepatocellular Carcinoma Via LGR5 Mediated β-Catenin and c-Myc Signaling

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 718 ◽  
Author(s):  
Koo ◽  
Lee ◽  
Jung ◽  
Im ◽  
Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Carcinoma Cells ◽  
Specific Protease ◽  
Hep3b Cells

In the current study, the function of long noncoding RNA (LncRNA) RAB5IF was elucidated in hepatocellular carcinoma (HCCs) in association with LGR5 related signaling. Here TCGA analysis revealed that LncRNA RAB5IF was overexpressed in HCC, and its overexpression level was significantly (p < 0.05) correlated with poor prognosis in patients with HCC. Furthermore, LncRNA RAB5IF depletion suppressed cell proliferation and colony formation, increased sub G1 population, cleavage of poly ADP-ribose polymerase (PARP) and cysteine aspartyl-specific protease (caspase 3) and attenuated the expression of procaspase 3, pro-PARP and B-cell lymphoma 2 (Bcl-2) in HepG2 and Hep3B cells. Furthermore, LncRNA RAB5IF depletion reduced the expression of LGR5 and its downstreams such as β-catenin and c-Myc in HepG2 and Hep3B cells. Notably, LGR5 depletion also attenuated the expression of pro-PARP, pro-caspase3, β-catenin and c-Myc in HepG2 and Hep3B cells. Conversely, LGR5 overexpression upregulated β-catenin and c-Myc in Alpha Mouse Liver 12 (AML-12) normal hepatocytes. Overall, these findings provide novel evidence that LncRNA RAB5IF promotes the growth of hepatocellular carcinoma cells via LGR5 mediated β-catenin and c-Myc signaling as a potent oncogenic target.

scholarly journals SENP2 Reduces Hepatocellular Carcinoma Stemness and Improves Sorafenib Sensitivity Through Inactivating the AKT/GSK3β/CTNNB1 Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaohui Tang ◽  
Bohao Liu ◽  
Chen Zhang ◽  
Wenbin Tang ◽  
Shitian Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Cell Counting ◽  
Normal Human Liver ◽  
Hep3b Cells ◽  
Plasmid Transfection ◽  
Sphere Formation ◽  
Cell Proportion

BackgroundSmall ubiquitin-like modifier specific peptidase 2 (SENP2) suppresses the progression and chemoresistance of several cancers, while few studies report its role in hepatocellular carcinoma (HCC). This study aimed to evaluate the effect of SENP2 on stemness, sorafenib sensitivity, and downstream pathway in HCC, with validation of its molecular mechanisms by compensation experiment.MethodsSENP2 was regulated by plasmid transfection; meanwhile, in a compensation experiment, protein kinase B (AKT) was activated by SC79 treatment and β-catenin (CTNNB1) was overexpressed by plasmid transfection. After modification, sorafenib sensitivity was detected by cell counting kit-8 assay; stemness was evaluated by CD133+ cell proportion and sphere formation assay.ResultsSENP2 was decreased in HCC cell lines (including Hep3B, Li7, and Huh7) compared with normal human liver epithelial cell lines, which was further reduced in HCC stem cells than in normal HCC cells. Subsequently, SENP2 overexpression inhibited CD133+ cell proportion, decreased sphere formation ability, promoted sorafenib sensitivity, suppressed AKT and glycogen synthase kinase-3β (GSK3β) phosphorylation, and reduced CTNNB1 expression in Huh7 and Hep3B cells, while SENP2 knockdown showed the reverse effects. The following compensation experiment revealed that activating AKT or overexpressing CTNNB1 promoted CD133+ cell proportion and sphere formation ability but suppressed sorafenib sensitivity in Huh7 and Hep3B cells. Moreover, activating AKT or overexpressing CTNNB1 attenuated the effect of SENP2 overexpression on stemness and sorafenib sensitivity in Huh7 and Hep3B cells.ConclusionSENP2 suppresses HCC stemness and increases sorafenib sensitivity through inactivating the AKT/GSK3β/CTNNB1 signaling pathway.

Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

RSC Advances ◽  
2015 ◽  
Vol 5 (83) ◽  
pp. 67996-68002 ◽  
Author(s):  
Ruqaiyah Khan ◽  
Imran Kazmi ◽  
Muhammad Afzal ◽  
Fahad A. Al Abbasi ◽  
Gohar Mushtaq ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Wistar Rats ◽  
Survival Rates ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Liver Carcinogenesis ◽  
The Third ◽  
Dose Combination

Hepatocellular carcinoma (HCC) is among the most lethal cancers (five-year survival rates under 11%), which makes it the third most frequent cause of cancer related deaths in men and sixth in women.

SYNTHESIS AND CYTOTOXICITY OF POLYHYDROXYLATED CHOLESTEROL DERIVATIVES

2018 ◽  
Vol 56 (4) ◽  
pp. 467
Author(s):  
Thu Thuy Thi Tran ◽  
Ha Thi Dinh ◽  
Phương Lan Doan ◽  
Long Quoc Pham ◽  
Quang Dai Ngo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Addition Compound ◽  
Hep G2 ◽  
Physical Methods ◽  
Hepatocellular Carcinoma Cell Line ◽  
Human Hepatocellular Carcinoma Cell ◽  
Hepatocellular Carcinoma Cell

Eight polyhydroxylated cholesterol derivatives (1-8) were prepared from cholesterol, using oxidative reagents as SeO2, OsO4/NMO, HCOOH/H2O2 and BH3/ H2O2. Their structures were elucidated by using physical methods including NMR 1D and 2D. These compounds were evaluated against two cancer cell lines (Hep-G2, T98). Compounds 2, 4 and 8 inhibits human hepatocellular carcinoma cell line (Hep-G2) with IC50 4.69, 4.98 and 2.89 µg/mL, respectively. In addition, compound 8 exhibited strong cytotoxicity against T98 cell line (glioblastoma) with IC50 = 2.28 μM.

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