scholarly journals The Effect of Kynurenic Acid on Apoptosis in Hepatocellular Carcinoma

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 6
Author(s):  
Atalay ◽  
Imamoglu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Glutamate Receptors ◽  
Hepg2 Cells ◽  
Kynurenic Acid ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Antitumor Effects ◽  
Glutamate Antagonists ◽  
Effector Caspase

Kynurenic Acid (KYNA) is a metabolite of tryptophan pathway and also an endogenous antagonist of glutamate receptors. Several studies indicated that glutamate antagonists have anti-proliferative potential. Moreover, subunits of the NMDA receptor which is one of the glutamate receptors have been shown to be found in human hepatocellular carcinoma cell line (HepG2). In this study, the antitumor effects of KYNA in HepG2 cells were investigated for the first time at the molecular level. The effects of KYNA on the viability of HepG2 cells were determined by MTT analyses. Effects of KYNA on mRNA transcriptions of apoptosis related genes Bax, Bcl-2 and Caspase-3 were analyzed by qRT-PCR. mRNA expression analysis revealed that the mRNA levels of effector Caspase-3 and pro-apoptotic Bax/Bcl-2 ratio were not increased in HepG2 cells treated with KYNA. In conclusion, our findings showed that KYNA does not exert its anti-proliferative effects on HepG2 cells through caspase-mediated apoptotic cell death, but it may perform this anti-proliferative effect through a different mechanism of death. Further studies are needed to find out potential cell death mechanisms that may play a role in anti-proliferative activity of KYNA on HepG2 cells.

The Antitumor Effects of Britanin on Hepatocellular Carcinoma Cells and its Real-Time Evaluation by In Vivo Bioluminescence Imaging

2020 ◽  
Vol 20 (9) ◽  
pp. 1147-1156
Author(s):  
Hanrui Li ◽  
GeTao Du ◽  
Lu Yang ◽  
Liaojun Pang ◽  
Yonghua Zhan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Blot Analysis ◽  
Tumor Size ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Bioluminescence Imaging ◽  
Antitumor Effects ◽  
In Vivo Bioluminescence Imaging

Background: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.

Study of the antineoplastic effect of modulating apoptosis-related noncoding RNA in human hepatocellular carcinoma cell line (HepG2)

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mai Abdel Azeem Sherif ◽  
Emtiaz Abd-elkawy Ismail ◽  
Samar Kamal Kassim ◽  
Hanan Hussein Shehata ◽  
Marwa Ali Abdel Khalek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Control Group ◽  
Antineoplastic Effect ◽  
And Control ◽  
Hcc Cells ◽  
Liver Tissues

Abstract MiR-421 is considered an important molecule that can prevent tumor growth. Bioinformatics analysis indicated that mRNA caspase-3 gene is a target gene of miR-421. The current study aimed to explore the functional role of miR-421 in hepatocellular carcinoma (HCC) and explore the interaction between miR-421 and caspase-3. To validate bioinformatics data, RT-qPCR was used to detect the expression of miR-421 and caspase-3 in 10 HCC tissues. The results showed miR-421 expression was significantly higher in HCC than non HCC liver tissues (P<0.01), nevertheless caspase-3 gene expression was markedly lower in HCC than non HCC liver tissues (P<0.01). Besides, miR-421 expression was negatively associated with caspase-3 expression. MiR-421 mimic and inhibitor was transfected into HCC cell lines (HepG2). Proliferation assay, showed that low-expression of miR-421 inhibited the proliferation of HCC cells. RT-qPCR was worked for detection the expression levels of miR-421 and caspase-3 in HepG2 cells before and after transfection. The results showed that miR-421 expression in HepG2 cells was significantly lower in miR-421 inhibitor transfected group than in mimic- transfected and control groups (Mock) (P≤ 0.05), and caspase-3 gene expression in HCC tissues was markedly higher in inhibitor transfected group than those transfected by mimic and control group (Mock) (P≤0.05). Thus, miR-421 inhibitor may inhibit the proliferation of HCC cells via over- expression of caspase-3.

scholarly journals O-GlcNAc Transferase Inhibitor Synergistically Enhances Doxorubicin-Induced Apoptosis in HepG2 Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3154
Author(s):  
Su Jin Lee ◽  
Oh-Shin Kwon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Hepg2 Cells ◽  
Drug Targets ◽  
Apoptotic Cell ◽  
Chemotherapy Resistance ◽  
Apoptotic Cell Death ◽  
Induced Apoptosis ◽  
Glcnac Transferase

The combination of chemotherapy with chemosensitizing agents is a common approach to enhance anticancer activity while reducing the dose-dependent adverse side effects of cancer treatment. Herein, we investigated doxorubicin (DOX) and O-GlcNAc transferase (OGT) inhibitor OSMI-1 combination treatment, which significantly enhanced apoptosis in hepatocellular carcinoma cells (HepG2) as a result of synergistic drug action in disparate stress signaling pathways. Treatment with a low dose of DOX or a suboptimal dose of OSMI-1 alone did not induce apoptotic cell death in HepG2 cells. However, the combination of DOX with OSMI-1 in HepG2 cells synergistically increased apoptotic cell death through the activation of both the p53 and mitochondrial Bcl2 pathways compared to DOX alone. We also demonstrated that the combination of DOX and OSMI-1 stimulated cell death, dramatically reducing cell proliferation and tumor growth in vivo using a HepG2 xenograft mouse model. These findings indicate that OSMI-1 acts as a potential chemosensitizer by enhancing DOX-induced cell death. This study provides insight into a possible mechanism of chemotherapy resistance, identifies potential novel drug targets, and suggests that OGT inhibition could be utilized in clinical applications to treat hepatocellular carcinoma as well as other cancer types.

scholarly journals An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Doaa E. Ahmed ◽  
Fatma B. Rashidi ◽  
Heba K. Abdelhakim ◽  
Amr S. Mohamed ◽  
Hossam M. M. Arafa
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Membrane Potential ◽  
Hepg2 Cells ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Caspase 9 ◽  
First Time ◽  
Bcl2 Gene

Abstract Background Glufosfamide (β-d-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-d-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model. Methods Cytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay. Results Glufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide. Conclusions The current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.

scholarly journals NeosedumosideIII induced Apoptosis of Human Hepatocellular Carcinoma HepG2 cells and SMMC-7721 Cells and Related Mechanism

2021 ◽  
Author(s):  
Xin-Yu Li ◽  
Xin Zhou ◽  
Yu- Liu ◽  
Feng Qiu ◽  
Qing-Qing Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Induced Apoptosis

Abstract Purpose: NeosedumosideIII (Neo) is a megastigmanes and belongs to monocyclic sesquiterpenoids compound with antioxidant, anti-inflammatory and other pharmacological activities. In order to explore the anti-cancer effect and possible mechanism of Neo, the study examined the anti-proliferation and apoptosis effect of Neo against human hepatocellular carcinoma HepG2 cells and SMMC-772 cells and related mechanism in vitro. Methods ：The anti-proliferation effect of Neo was detected on HepG2 cells and SMMC-772 cells by MTT assay and IC50 with increasing dose and time. Cell cycle and apoptosis were detected by flow cytometer. The changes of Bcl-2, Bax, Caspase-3, Caspase-8 and Caspase-9 proteins were detected by western blotting.Results ：The results indicated that Neo could inhibited proliferation of HepG2 cells and SMMC-772 cells in vitro and promoted apoptosis, it significantly induced apoptosis of HepG2 cells and SMMC-772 cells arrested cell cycle at G0/G1 phase in a dose-dependent manner, reduce the expression of Bcl-2 protein, and increase the expression of Bax and Caspase-3, Caspase-8 and Caspase-9 proteins. Conclusion：Neo could inhibit proliferation and induce apoptosis of HepG2 cells and SMMC-7721 cells in vivo which suggested that it might be served as a promising candidate for the treatment of liver cancer.

scholarly journals Bioactivity Screening of Antarctic Sponges Reveals Anticancer Activity and Potential Cell Death via Ferroptosis by Mycalols

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 459
Author(s):  
Gennaro Riccio ◽  
Genoveffa Nuzzo ◽  
Gianluca Zazo ◽  
Daniela Coppola ◽  
Giuseppina Senese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Hepg2 Cells ◽  
Iron Homeostasis ◽  
Protein Levels ◽  
Antarctic Research ◽  
First Time ◽  
Antarctic Sponges

Sponges are known to produce a series of compounds with bioactivities useful for human health. This study was conducted on four sponges collected in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018, i.e., Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemimycale topsenti, and Hemigellius pilosus. Sponge extracts were fractioned and tested against hepatocellular carcinoma (HepG2), lung carcinoma (A549), and melanoma cells (A2058), in order to screen for antiproliferative or cytotoxic activity. Two different chemical classes of compounds, belonging to mycalols and suberitenones, were identified in the active fractions. Mycalols were the most active compounds, and their mechanism of action was also investigated at the gene and protein levels in HepG2 cells. Of the differentially expressed genes, ULK1 and GALNT5 were the most down-regulated genes, while MAPK8 was one of the most up-regulated genes. These genes were previously associated with ferroptosis, a programmed cell death triggered by iron-dependent lipid peroxidation, confirmed at the protein level by the down-regulation of GPX4, a key regulator of ferroptosis, and the up-regulation of NCOA4, involved in iron homeostasis. These data suggest, for the first time, that mycalols act by triggering ferroptosis in HepG2 cells.

scholarly journals Inhibitory effect and mechanism of action (MOA) of hirsutine on the proliferation of T-cell leukemia Jurkat clone E6-1 cells

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10692
Author(s):  
Jie Meng ◽  
Rui Su ◽  
Luping Wang ◽  
Bo Yuan ◽  
Ling Li
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Death ◽  
T Cell ◽  
Mechanism Of Action ◽  
Mrna Levels ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antitumor Effects

Background The bark of Uncaria rhynchophylla has been traditionally used to treat convulsion, bleeding, hypertension, auto-immune conditions, cancer, and other diseases. The main focus of this research is done for the purpose of exploring the antitumor activity and mechanism of action (MOA) for hirsutine isolated from U. rhynchophylla. Methods Jurkat clone E6-1 cells were treated using 10, 25 and 50 μM for 48 h. Inhibition of cell proliferation due to hirsutine treatment was evaluated by CCK8 assay. Flow cytometry was applied to ascertain Jurkat cell cycle progression and apoptosis after treatment with 10, 25 and 50 μM hirsutine for 48 h. The expression and level of the apoptosis-related genes and proteins was analyzed by Real-time Quantitative polymerase chain reaction (qPCR) and Western blotting method, respectively. Results CCK8 analyses revealed that hirsutine could significantly inhibit the proliferation of Jurkat clone E6-1 cells, in a concentration and time-dependent fashion. Flow cytometry assays revealed that hirsutine could drive apoptotic death and G0/G1 phase arrest in Jurkat cells. Apoptotic cells frequencies were 4.99 ± 0.51%, 13.69 ± 2.00% and 40.21 ± 15.19%, and respective cell cycle arrest in G0/G1 accounted for 34.85 ± 1.81%, 42.83 ± 0.70% and 49.12 ± 4.07%. Simultaneously, compared with the control group, Western blot assays indicated that the up-regulation of pro-apoptotic Bax, cleaved-caspase3, cleaved-caspase9 and Cyto c proteins, as well as the down-regulation of Bcl-2 protein which guards against cell death, might be correlated with cell death induction and inhibition of cell proliferation. QPCR analyses indicated that hirsutine could diminish BCL2 expression and, at the same time, improve Bax, caspase-3 and caspase-9 mRNA levels, thus reiterating a putative correlation of hirsutine treatment in vitro with apoptosis induction and inhibition of cell proliferation (p-value < 0.05). Excessive hirsutine damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in Jurkat clone E6-1 cells, thereby inducing the activated caspase cascade apoptosis process through a mitochondria-mediated pathway. Conclusion An important bioactive constituent—hirsutine—appears to have antitumor effects in human T-cell leukemia, thus enlightening the use of phytomedicines as a novel source for tumor therapy. It is speculated that hirsutine may induce apoptosis of Jurkat Clone E6-1 cells through the mitochondrial apoptotic pathway.

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

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