scholarly journals In Vitro Cytotoxicity Activity of Ethanolic Leaf Extract of Costus Igneus Against Hepatocellular Carcinoma (HepG2) Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 901-906
Author(s):  
I. Glory Josephine ◽  
K. Punnagai
Keyword(s):  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Anticancer Activity ◽  
Hepg2 Cells ◽  
Ethanolic Extract ◽  
In Vitro Cytotoxicity ◽  
Alcoholic Fatty Liver ◽  
Cytotoxicity Activity ◽  
Costus Igneus

Costus igneus popularly known as ‘Insulin plant’ belongs to Costaceae family. The anti diabetic potential of the plant has been evaluated and widely used as Ayurvedic medicinal herb to treat diabetes mellitus and associated metabolic syndrome. Recently Non- alcoholic fatty liver disease (NAFLD) associated metabolic syndrome has been identified as an important risk factor for hepatocellular carcinoma (HCC). So agents with insulin sensitizing action could play dual role in the control of metabolic syndrome and cancer. This study is designed to evaluate the in vitro anticancer activity of the ethanolic extract of Costus igneus leaves against hepatocellular carcinoma( HepG2) cells. The viable cells were assessed by cytotoxicity activity (MTT assay) with the eight different concentration (1000 to7.8μg/ml) of the extracts. The percentage of viability was calculated. From the graph the concentration required for a 50% of viability (IC50) was calculated as 62.5μg/ml. However 74.57% and 22.65% of cell viability were produced by the concentration of 7.8μg/ml and 1000μg/ml respectively. The results showed the cytotoxic activity of ethanolic extract of Costus igneus leaves and proved the anticancer activity against liver cancer cells.

Combination of Zizyphus jujuba and Green Tea Extracts Exerts Excellent Cytotoxic Activity in HepG2 Cells via Reducing the Expression of APRIL

2009 ◽  
Vol 37 (01) ◽  
pp. 169-179 ◽  
Author(s):  
Xuedan Huang ◽  
Akiko Kojima-Yuasa ◽  
Shenghui Xu ◽  
David Opare Kennedy ◽  
Tadayoshi Hasuma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Anticancer Activity ◽  
Green Tea ◽  
Hepg2 Cells ◽  
Chemotherapeutic Agents ◽  
Chloroform Fraction ◽  
The Future ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

Hepatocellular carcinoma is a type of tumor highly resistant to available chemotherapeutic agents. The treatment of hepatocellular carcinoma remains a challenge that needs new approaches in the future. In a previous study, we demonstrated that the chloroform fraction (CHCl3-F) from Z. jujuba has anticancer activity in human liver cancer cells (HepG2), and that combining CHCl3-F with green tea extracts (GTE) results in enhanced effects of anticancer activity in the cells. To further understand the mechanism of the anticancer activity of combining CHCl3-F and GTE in HepG2 cells, we investigated whether the addition of a mixture of CHCl3-F and GTE would affect the expression of APRIL (a proliferation-inducing ligand), which was expressed in HepG2 cells from 4 hours of incubation in vitro. We have shown that CHCl3-F and GTE enhanced anti-cancer activity by reducing the expression of APRIL. We speculate that the CHCl3-F and GTE mixture might provide a lead to a new drug design to treat hepatocellular carcinoma in the future.

scholarly journals The SGLT2 Inhibitor Canagliflozin Prevents Carcinogenesis in a Mouse Model of Diabetes and Non-Alcoholic Steatohepatitis-Related Hepatocarcinogenesis: Association with SGLT2 Expression in Hepatocellular Carcinoma

2019 ◽  
Vol 20 (20) ◽  
pp. 5237 ◽  
Author(s):  
Teruo Jojima ◽  
Sho Wakamatsu ◽  
Masato Kase ◽  
Toshie Iijima ◽  
Yuko Maejima ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Model ◽  
Hepg2 Cells ◽  
Liver Tumors ◽  
Sglt2 Inhibitor ◽  
In Vitro Study ◽  
Vehicle Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis

The aim of the present study is to investigate the effects of canagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, on non-alcoholic steatohepatitis (NASH) and NASH-related hepatocellular carcinoma (HCC) in a mouse model of diabetes and NASH-HCC. First, mice aged five weeks were divided into two groups (vehicle group and canagliflozin group) and were treated for three weeks. Then, mice aged five weeks were divided into three groups of nine animals each: the vehicle group, early canagliflozin group (treated from five to nine weeks), and continuous canagliflozin group (treated from five to 16 weeks). Canagliflozin was administered at a dose of 30 mg/kg in these experiments. In addition, the in vitro effects of canagliflozin were investigated using HepG2 cells, a human HCC cell line. At the age of eight or 16 weeks, the histological non-alcoholic fatty liver disease activity score was lower in the canagliflozin-treated mice than in vehicle-treated mice. There were significantly fewer hepatic tumors in the continuous canagliflozin group than in the vehicle group. Immunohistochemistry showed significantly fewer glutamine synthetase-positive nodules in the continuous canagliflozin group than in the vehicle group. Expression of α-fetoprotein mRNA, a marker of HCC, was downregulated in the continuous canagliflozin group when compared with the vehicle group. At 16 weeks, there was diffuse SGLT1 expression in the hepatic lobules and strong expression by hepatocytes in the vehicle group, while SGLT2 expression was stronger in liver tumors than in the lobules. In the in vitro study, canagliflozin (10 μM) suppressed the proliferation of HepG2 cells. Flow cytometry showed that canagliflozin reduced the percentage of HepG2 cells in the G2/M phase due to arrest in the G1 phase along with decreased expression of cyclin D and Cdk4 proteins, while it increased the percentage of cells in the G0/1 phase. Canagliflozin also induced apoptosis of HepG2 cells via activation of caspase 3. In this mouse model of diabetes and NASH/HCC, canagliflozin showed anti-steatotic and anti-inflammatory effects that attenuated the development of NASH and prevented the progression of NASH to HCC, partly due to the induction of cell cycle arrest and/or apoptosis as well as the reduction of tumor growth through the direct inhibition of SGLT2 in tumor cells.

scholarly journals Evaluation of Cytotoxic Activity in Ethanolic Extract of Cucumis melo (L). fruit

2020 ◽  
Vol 2 (1) ◽  
pp. 70
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Hepg2 Cells ◽  
Cucumis Melo ◽  
Ethanolic Extract ◽  
In Vitro Cytotoxicity ◽  
Cucumis Melo L

Cytotoxicity is the quality of being toxic to cells, and in vitro cytotoxicity testing procedures reduce the use of laboratory animals. The present study was designed to investigate the cytotoxic activity of the Cucumis melo (L) fruit against HepG2 cell lines. To prepare the extract, fresh pulps of Cucumis melo fruit was chopped into pieces and dried at room temperature for 24 hours. 10 g of the dried fruit powder was successively extracted with 100 ml of ethanol using Soxhlet apparatus and filtered through Whatman No 1 filter paper. The cytotoxic activity for cancer cell lines was evaluated by MTT assay. The in vitro cytotoxicity of different concentrations (18.75 - 300μg/mL) of the ethanolic extract of Cucumis melo fruit was evaluated by the MTT assay. The IC50 value is measured by the concentration of extract, causing 50% growth inhibition of cancer cells. The results indicated that the cytotoxic effect of the ethanolic extract of Cucumis melo fruit against HepG2 cells is dose-dependent. At low concentrations, the extract was found to be less toxic towards the HepG2 cells, whereas, at higher concentrations, the toxicity was increased. The concentration at 201.5 µg / ml was found to be an effective dose because, at this concentration, it exhibited 50 % cytotoxicity against HepG2 cells. This work revealed the potentials of ethanolic extract of Cucumis melo fruit as a cytotoxic agent against liver cancer cell lines. The plant can be further screened against various diseases using toxicity models in order to find out its unexplored efficacy.

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

scholarly journals Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie Jacques ◽  
Arash Arjomand ◽  
Hélène Perée ◽  
Patrick Collins ◽  
Alice Mayer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Damage ◽  
Chow Diet ◽  
Serum Triglycerides ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice

2020 ◽  
Vol 39 (11) ◽  
pp. 1528-1544 ◽  
Author(s):  
HE Abo Mansour ◽  
MM El-Batsh ◽  
NS Badawy ◽  
ET Mehanna ◽  
NM Mesbah ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Anticancer Activity ◽  
Hepg2 Cells ◽  
Chitosan Nanoparticles ◽  
B Cell Lymphoma ◽  
Favorable Effect ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Endothelial Growth Factor

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups ( n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

Synthesis, characterization and in vitro cytotoxicity of gold(iii) dialkyl/diaryldithiocarbamato complexes

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81599-81607 ◽  
Author(s):  
Muhammad Altaf ◽  
Anvarhusein A. Isab ◽  
Ján Vančo ◽  
Zdeněk Dvořák ◽  
Zdeněk Trávníček ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Vitro Cytotoxicity ◽  
Methyl Ethyl

A series of six dialkyl/diaryldithiocarbamato (dtc) gold(iii) complexes [Au(R2dtc)2]Cl (1,3, and5), and [Au(R2dtc)Cl2] (2,4, and6), (R = methyl, ethyl, and benzyl) was synthesised and evaluated for anticancer activity with promising results (EC50≈ 9.5 μM).

scholarly journals Potential Role of microRNA-183 as a Tumor Suppressor in Hepatocellular Carcinoma

2018 ◽  
Vol 51 (5) ◽  
pp. 2065-2072 ◽  
Author(s):  
Wei Bian ◽  
Hongfei Zhang ◽  
Miao Tang ◽  
Shaojun Zhang ◽  
Lichao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Reporter Assays

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document