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.

Involvement of NF-κB activation in the apoptosis induced by extracellular adenosine in human hepatocellular carcinoma HepG2 cellsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 705-714 ◽  
Author(s):  
Ling-Fei Wu ◽  
Guo-Ping Li ◽  
Jian-Dong Su ◽  
Ze-Jin Pu ◽  
Jia-Lin Feng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Mtt Assay ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner

Adenosine can exhibit cytotoxic activity in vivo and in vitro, though its mechanisms are still uncertain. In this study, we investigated the adenosine-mediated apoptotic signaling pathway and the role of NF-κB in human hepatocellular carcinoma HepG2 cells. HepG2 cells were treated with different concentrations of adenosine for 12–48 h, and the effect of adenosine on cell proliferation was evaluated by MTT assay. The cytotoxicity of adenosine alone or in combination with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), was also evaluated by MTT assay and the mode of cell death was detected by Hoechst 33342 staining. Cell cycle progress was performed by flow cytometry with PI staining. The protein expressions of Bcl-2, p53, NF-κB subunit p65, and caspase-3 were assayed by Western blot. Caspase-3 activity was measured by spectrophotomteric assay. The results showed that adenosine significantly reduced the viability of HepG2 cells in a dose- and time-dependent manner, with IC 50 (24 and 48 h) of 2.52 and 1.89 mmol·L–1, respectively. The apoptotic index (percentage of sub-G1 phase) of HepG2 cells in adenosine treatment alone for 12 and 24 h or in combination with PDTC were 8.30%, 22.32% and 20.18%, 30.89%, respectively. All of them were higher than that in the control group (0.81%, p < 0.01). The characteristic changes of cell apoptosis (chromatin condensation and sub-G1 peak) were observed under fluorescent microscopy and flow cytometry. We also found that the apoptotic process triggered by adenosine was involved in G0–G1 cell-cycle arrest, enhanced the activity of caspase-3, upregulated p53 and NF-κB p65 expression, and downregulated Bcl-2 expression. Inhibition of NF-κB by PDTC decreased NF-κB p65 expression, enhanced cell apoptosis ratio, and increased caspase-3 activity. NF-κB may play an anti-apoptosis role in adenosine-induced HepG2 cytotoxicity.

scholarly journals Autoregulatory Feedback Mechanism of P38MAPK/Caspase-8 in Photodynamic Therapy-Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Induced Apoptosis of Human Hepatocellular Carcinoma Bel-7402 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Wang ◽  
Chunhui Xia ◽  
Wei Chen ◽  
Yuhang Chen ◽  
Yiyi Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Photodynamic Therapy ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Induced Apoptosis

Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Our previous study showed that hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy) phthalocyanine zinc- (TαPcZn-) mediated PDT (TαPcZn-PDT) inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle. However, mechanisms of TαPcZn-PDT-induced apoptosis of Bel-7402 cells have not been fully clarified. In the present study, therefore, effect of TαPcZn-PDT on apoptosis, P38MAPK, p-P38MAPK, Caspase-8, Caspase-3, Bcl-2, Bid, Cytochrome c, and mitochondria membrane potential in Bel-7402 cells without or with P38MAPK inhibitor SB203580 or Caspase-8 inhibitor Ac-IEFD-CHO was investigated by haematoxylin and eosin (HE) staining assay, flow cytometry analysis of annexin V-FITC/propidium iodide (PI) double staining cells and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and immunoblot assay. We found that TαPcZn-PDT resulted in apoptosis induction, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. In contrast, SB203580 or Ac-IEFD-CHO attenuated induction of apoptosis, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. Taken together, we conclude that Caspase-3, Bcl-2, Bid, and mitochondria are involved in autoregulatory feedback of P38MAPK/Caspase-8 during TαPcZn-PDT-induced apoptosis of Bel-7402 cells.

Arsenic trioxide–induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 4078-4087 ◽  
Author(s):  
Qun Liu ◽  
Susan Hilsenbeck ◽  
Yair Gazitt
Keyword(s):  
Cell Cycle ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Myeloma Cells ◽  
Induced Apoptosis ◽  
In Cells

Abstract Arsenic trioxide (ATO) has been shown to induce differentiation and apoptosis in acute promyelocytic leukemia (APL) cells concomitant with down-regulation of the PML-RARα fusion protein, a product of the t(15:17) translocation characteristic of APL leukemic cells. However, ATO is also a potent inducer of apoptosis in a number of other cancer cells lacking the t(15:17) translocation. The exact mechanism of ATO-induced apoptosis in these cells is not yet clear. We tested the effect of ATO on 7 myeloma cell lines with varying p53 status and report that in cells with mutated p53, ATO induced rapid and extensive (more than 90%) apoptosis in a time- and dose-dependent manner concomitant with arrest of cells in G2/M phase of the cell cycle. Myeloma cells with wild-type (wt) p53 were relatively resistant to ATO with maximal apoptosis of about 40% concomitant with partial arrest of cells in G1 and up-regulation of p21. The use of caspase blocking peptides, fluorescence-tagged caspase-specific substrate peptides, and Western immunoblotting confirmed the involvement of primarily caspase-8 and -3 in ATO-induced apoptosis in myeloma cells with mutated p53 and primarily caspase-9 and -3 in cells expressing wt p53. We also observed up-regulation by ATO of R1 and R2 APO2/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) receptors. Most important, however, we observed a synergy between ATO and APO2/TRAIL in the induction of apoptosis in the partially resistant myeloma cell lines and in myeloma cells freshly isolated from myeloma patients. Our results justify the use of the combination of these 2 drugs in clinical setting in myeloma patients.

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 Anticancer Activity of Smallanthus sonchifolius Methanol Extract against Human Hepatocellular Carcinoma Cells

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3054 ◽  
Author(s):  
Phyu Phyu Myint ◽  
Thien T. P. Dao ◽  
Yeong Shik Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cell Line ◽  
Methanol Extract ◽  
Herbal Remedy ◽  
Human Hepatocellular Carcinoma ◽  
Dependent Manner ◽  
Smallanthus Sonchifolius

Background: This research aimed to investigate the cytotoxicity of methanol extract of Smallanthus sonchifolius leaf (YLE) against a human hepatocellular carcinoma cell line (HepG2). This plant is currently used as a traditional herbal remedy in the treatment of liver diseases in some rural parts of Myanmar. Methods: The cytotoxic activity of the plant extract against the cancerous cell line was assessed using an MTT assay. YLE demonstrated a significant effect (IC50 = 58.2 ± 1.9 μg/mL) on anti-cancer activity, which was further investigated using various assays including an in vitro cell migration assay, a colony formation assay, cell cycle analysis, western blot analysis, and a ROS assay. The significance of the phytochemical constituents of YLE could be identified using LC/Q-TOF-MS techniques. Results: We putatively identified the active components in YLE, which were possibly melampolide-type sesquiterpenoids. YLE showed an inhibitory effect on HepG2 cell proliferation and cell migration. YLE also induced cell cycle arrest and necrosis in a dose-dependent manner. Additionally, YLE significantly suppressed ROS formation in HepG2 cells. Conclusions: These findings suggest that YLE is sufficient for application as a promising anti-liver drug in herbal medicine.

Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Erianin Involves a Mitochondria-Mediated Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 261-269
Author(s):  
Zhong Min ◽  
He Lei ◽  
Shi Yujie ◽  
Chen Xin ◽  
Ren Jianwu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Activity ◽  
Hepg2 Cells ◽  
Chinese Herb ◽  
Human Hepatocellular Carcinoma ◽  
Dependent Manner ◽  
M Cell ◽  
Cytochrome C Release ◽  
Intracellular Ca ◽  
Induced Apoptosis

Erianin is a natural product derived from the traditional Chinese herb, Dendrobium chrysotoxum, which is highly valued for its antitumor activity in various cancer cells. However, the specific mechanism of antitumor activity of erianin in human hepatocellular carcinoma remains unclear. This study aimed to investigate erianin-induced apoptosis in human hepatocellular carcinoma HepG2 cells. The proliferation of HepG2 cells was significantly inhibited by the treatment of erianin in a doseand time-dependent manner. In addition, erianin induced a series of apoptosis-related events in HepG2 cells, including G2/M cell cycle arrest, the loss of the mitochondrial membrane potential, elevation of intracellular Ca2+, and accumulation of reactive oxygen species. Erianin activated the caspase-3 and caspase-9 without a change in caspase-8, accompanied by upregulation of the expression of Bax and downregulation of the expression of Bcl-2 along with cytochrome C release from the mitochondria. There was no significant change in Fas and FasL expression, indicating that the exogenous pathway is not involved in erianin-induced apoptosis. In summary, it concluded that erianin-induced apoptosis in HepG2 cells is through a mitochondria-mediated pathway. The results of this study suggest that erianin may serve as a novel therapeutic agent for the treatment of human hepatocellular carcinoma in the future.

Compressive Force Induces Osteoblast Apoptosis via Caspase-8

2006 ◽  
Vol 85 (3) ◽  
pp. 240-244 ◽  
Author(s):  
Y. Goga ◽  
M. Chiba ◽  
Y. Shimizu ◽  
H. Mitani
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Osteoblast Apoptosis

Periodontal remodeling during orthodontic tooth movement is a result of mechanical stresses. The application of excessive orthodontic force induces cell death. However, the nature of compressive force-induced cell death is unclear. We examined whether the in vitro application of continuous compressive force would induce apoptosis in human osteoblast-like cells (MG-63 cells), and investigated the mechanism by which apoptosis was initiated. The cells became aligned irregularly, and cell viability decreased, indicating that the compressive force caused cell death. According to the TUNEL analysis, the number of apoptotic cells increased significantly in a time-and force-dependent manner. Caspase-3 activity increased with the magnitude of the compressive force, and this effect was reduced significantly by a caspase-8 inhibitor, whereas a caspase-9 inhibitor had no such effect. We conclude that the in vitro application of compressive force can induce apoptosis in MG-63 cells through the activation of caspase-3 via the caspase-8 signaling cascade.

scholarly journals Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner

2008 ◽  
Vol 89 (8) ◽  
pp. 1930-1941 ◽  
Author(s):  
Chang-Huei Tsao ◽  
Hong-Lin Su ◽  
Yi-Ling Lin ◽  
Han-Pang Yu ◽  
Shu-Ming Kuo ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Caspase 3 ◽  
Encephalitis Virus ◽  
Dominant Negative Mutant ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Effector Caspase ◽  
Induced Apoptosis

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, replicates primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected cells. This study investigated the hierarchical activation of the caspase network induced by JEV infection. It was found that JEV activated the initiators caspase-8 and -9, as well as effector caspase-3, in infected baby hamster kidney and mouse neuroblastoma (N18) cells. In neuronal N18 cells, JEV infection triggered cytochrome c release from mitochondria, which in turn activated caspase-9 and -3. Treatment of JEV-infected N18 cells with cyclosporin A or ruthenium red, which attenuate mitochondrial injuries, blocked activation of caspase-9 or -3, typifying that, in neuronal cells, this apoptosis involves the mitochondrial pathway. Alternatively, in caspase-3-deficient MCF-7 cells, JEV persisted and readily triggered a typical apoptotic response, including cytochrome c release and full activation of caspase-9 and -8 along with caspase-6, indicating that JEV did not require caspase-3 to manifest caspase-8 activation and apoptosis. Interestingly, a Fas-associated death-domain-containing protein (FADD) dominant-negative mutant, which interfered with transmission of the extracellular death signals into cells through the Fas/tumour necrosis factor (TNF) receptor, failed to block JEV-induced apoptosis and caspase-8 activation, implying that receptor oligomerization of the Fas/TNF pathway might not participate in JEV-induced apoptosis. Taken together, these results illustrate that JEV infection triggers caspase cascades involving the initiators caspase-8 and -9, probably through FADD-independent but mitochondrion-dependent pathways.

Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo

2017 ◽  
Vol 126 (5) ◽  
pp. 868-881 ◽  
Author(s):  
Wei Xing ◽  
Dong-Tai Chen ◽  
Jia-Hao Pan ◽  
Yong-Hua Chen ◽  
Yan Yan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Hepg2 Cells ◽  
Xenograft Model ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Bax Protein

Abstract Background Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied. Methods Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments. Results Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P &lt; 0.0001; lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin). Conclusions The authors’ findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.

Phenyhexyl Isothiocyanate, a Dual Inhibitor of Histone Deacetylation and Methylation, Inhibit Acute Lymphoblastic Leukemia Cells through Epigenetic Modulation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4532-4532
Author(s):  
Yiqun Huang ◽  
Xudong Ma ◽  
Dicky J.W. Chiao ◽  
Delong Liu
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
Caspase 3 ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Dual Inhibitor

Abstract We have shown that phenyhexyl isothiocyanate(PHI) is a novel histone deacetylase inhibitor and can also modulate histone methylation. In this study we investigated the effect of PHI on human Acute Lymphoblastic leukemia cell line Molt-4 in vitro. The viability of Molt-4 cells was determined by MTT method. Apoptosis and cell cycle arrest were measured by flow cytometry. The expression of bcl-2, caspase-9, caspase-8, caspase-3, PRAP protein, acetylated H3 and H4, methylated H3K9 and H3K4 were detected by Western Blotting. The results showed that PHI inhibited the cell growth and decreased viability of Molt-4 cells. Cell cycle analysis indicated an arrest in G0/G1 phase. The expression of bcl-2, caspase-9, caspase-3, and PRAP was inhibited by PHI in a dose and time dependent manner. In contrast, there was no significant change in the expression of Caspase-8. PHI also significantly increased the level of acetylated histone H3 as well as H4. Interestingly, PHI increased the level of methylated H3k4, but decreased methylated H3K9. These data suggest that ALL cells are sensitive to the novel HDAC inhibitor, and PHI may become a novel agent in ALL therapy.

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