scholarly journals Role of Apoptotic Proteins in REC-2006 Mediated Radiation Protection in Hepatoma Cell Lines

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Pankaj Kumar Singh ◽  
Raj Kumar ◽  
Ashok Sharma ◽  
Rajesh Arora ◽  
Raman Chawla ◽  
...  
Keyword(s):  
Radiation Protection ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Treated Group ◽  
Caspase 9 ◽  
Hepatoma Cell Lines ◽  
Hep3b Cells ◽  
Parp 1

The present study was carried out to evaluate the role of apoptotic proteins in REC-2006-mediated radiation protection in hepatoma cell lines. REC-2006 treatment 2 h before irradiation strongly inhibited the cleavage of ATM and PARP-1 in HepG2 cells. The expression of nuclear apoptosis inducing factor (AIF) was found to be more inhibited (~17%) in HepG2 cells in REC-2006 + radiation-treated group. More inhibition (~33%) of cytochromecwas observed in HepG2 cells upon REC-2006 treatment 2 h prior irradiation. Similarly, significantly more (P<.05) inhibition of Apaf-1, caspase-9 and caspase-3 was observed in REC-2006 + radition-treated group in HepG2 cells. REC-2006 treatment restored the expression of ICAD in HepG2 cells; however, no restoration was observed in Hep3B cells. Lower nuclear to cytoplasmic CAD ratio was observed in HepG2 cells (~0.6) as compared with Hep3B cells (~1.2) in REC-2006 + radiation-treated group. In conclusion, REC-2006 rendered higher protection in HepG2 cells by inhibiting the expression and translocation of AIF, inhibiting the cleavage of ATM and PARP-1, restoring the expression of ICAD, inhibiting the release of cytochromecand thus modulating the expression of Apaf-1 caspase-9 and activity of caspase-3.

Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis

2020 ◽  
Vol 20 (4) ◽  
pp. 504-517
Author(s):  
Yu-Lan Li ◽  
Xin-Li Gan ◽  
Rong-Ping Zhu ◽  
Xuehong Wang ◽  
Duan-Fang Liao ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cell ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Caspase 9

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

scholarly journals miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Gang Wu ◽  
Zhixi Li ◽  
Youyu Wang ◽  
Xueming Ju ◽  
Rui Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Luciferase Reporter ◽  
Hepatoma Cell Line ◽  
Novel Therapy ◽  
The Third ◽  
Direct Target

Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.

Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors

1991 ◽  
Vol 11 (1) ◽  
pp. 108-116
Author(s):  
I Zvibel ◽  
E Halay ◽  
L M Reid
Keyword(s):  
Growth Factor ◽  
Hepg2 Cells ◽  
Clonal Growth ◽  
Hepatoma Cell ◽  
Growth Efficiency ◽  
Tgf Beta ◽  
Mrna Synthesis ◽  
Hepatoma Cell Lines ◽  
Poorly Differentiated ◽  
Heparan Sulfates

Highly sulfated, heparinlike species of heparan sulfate proteoglycans, with heparinlike glycosaminoglycan chains, are extracellular matrix components that are plasma membrane bound in growth-arrested liver cells. Heparins were found to inhibit the growth and lower the clonal growth efficiency of HepG2, a minimally deviant, human hepatoma cell line. Heparan sulfates, closely related glycosaminoglycans present in the extracellular matrix around growing liver cells, had no effect on the growth rate or clonal growth efficiency of HepG2 cells. Neither heparins nor heparan sulfates had any effect on the growth rate or clonal growth efficiency of two poorly differentiated, highly metastatic hepatoma cell lines, SK-Hep-1 and PLC/PRF/5. Heparin's inhibition of growth of HepG2 cells correlated with changes in the mRNA synthesis and abundance of insulinlike growth factor II (IGF II) and transforming growth factor beta (TGF beta). HepG2 cells expressed high basal levels of mRNAs encoding IGF II and TGF beta that were inducible, through transcriptional and posttranscriptional mechanisms, to higher levels by specific heparin-hormone combinations. For both IGF II and TGF beta, the regulation was multifactorial. Transcriptionally, IGF II was regulated by the additive effects of insulin, glucagon, and growth hormone in combination with heparin; TGF beta was regulated primarily by the synergistic effects of insulin and growth hormone in combination with heparin. Posttranscriptionally, the mRNA abundance of the IGF II 4.5- and 3.7-kb transcripts was affected by insulin. Heparin induction of all IGF II transcripts was also dependent on triiodotyronine and prolactin, but it is unknown whether their induction by heparin was via transcriptional or posttranscriptional mechanisms. Heparin-insulin combinations regulated TGF beta posttranscriptionally. The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGF beta, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination. We discuss the data as evidence that matrix chemistry is a variable determining the expression of autocrine growth factor genes and the biological responses to them.

Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells

2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Death Receptor ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Death Receptor Pathway ◽  
L02 Cells

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.

scholarly journals Role of hydrogen peroxide in hypoxia-induced erythropoietin production

1994 ◽  
Vol 303 (2) ◽  
pp. 507-510 ◽  
Author(s):  
J Fandrey ◽  
S Frede ◽  
W Jelkmann
Keyword(s):  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Endogenous Production ◽  
Hepatoma Cell Line Hepg2 ◽  
Haem Protein ◽  
Exogenous H2o2

The addition of exogenous H2O2 inhibited hypoxia-induced erythropoietin (Epo) production in the human hepatoma cell line HepG2. Likewise, elevation of endogenous H2O2 levels by the addition of menadione or the catalase inhibitor, aminotriazole, dose-dependently lowered Epo production. The inhibitory effect of exogenous H2O2 on Epo formation could be completely overcome by co-incubation with catalase. When GSH levels in HepG2 cells were lowered, Epo production was more susceptible to H2O2-induced inhibition, indicating that H2O2 might affect thiol groups in regulatory proteins. Endogenous production of H2O2 in HepG2 cells was dependent on the pericellular O2 tension, being lowest under conditions of hypoxia. Our results support the hypothesis that an H2O2-generating haem protein might be part of the O2 sensor that controls Epo production. High H2O2 levels under conditions of normoxia suppress, whereas lower levels in hypoxic cells allow epo gene expression.

scholarly journals Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Tsen-Ni Tsai ◽  
Jia-Jing Ho ◽  
Maw-Shung Liu ◽  
Tzu-Ying Lee ◽  
Mei-Chin Lu ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Caspase 3 ◽  
Cecal Ligation ◽  
B Cell Lymphoma ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Glutamate Pyruvate ◽  
Serum Glutamate

This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.

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 Tetrastigma hemsleyanum flavones exert anti-hepatic carcinoma property both in vitro and in vivo

2021 ◽  
Author(s):  
Yangyang Liu ◽  
Yonglu Li ◽  
Wen Chen ◽  
Xiang Ye ◽  
Ruoyi Jia ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Caspase 3 ◽  
Expression Level ◽  
Caspase 9 ◽  
Tetrastigma Hemsleyanum ◽  
Tumor Bearing ◽  
And Migration ◽  
Proliferation And Migration

Abstract: Tetrastigma hemsleyanum has been regarded as an anticancer food in China. However, its corresponding mechanisms remains unclear. Thus, in this study, the antitumor activity of flavones-rich fraction of root of Tetrastigma hemsleyanum (FRTH) was investigated in vitro and in vivo. The results indicated that FRTH could inhibit the proliferation and migration of HepG2 cells in vitro by PI3K/AKT pathway. FRTH could increase the ROS level and change the mitochondrial membrane potential (MMP) in HepG2 cells. In addition, FRTH treatment (300, 600 mg/kg BW) significantly suppressed tumor growth on HepG2 tumor-bearing nude mice. Besides, immunohistochemistry assays and western blotting revealed that FRTH enhanced the expression level of Bax/Bcl-2, cytochrome C, Caspase-3, caspase-9, Cleaved-caspase-3, and downregulated the expression level of CD31, ki67 and VEGF in HepG2 tumor-bearing mice. Our study suggests Tetrastigma hemsleyanum as a promising candidate medicine for liver cancer treatment.

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.

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