Effects of Lidocaine-Mediated CPEB3 Upregulation in Human Hepatocellular Carcinoma Cell Proliferation In Vitro

Lidocaine displays antitumor activity by inducing apoptosis and suppressing tumor growth in human hepatocellular carcinoma (HepG2) cells in vitro. However, the molecular mechanism underlying lidocaine-mediated antitumor activity is unclear. In this study, HepG2 cells were treated with lidocaine, and cell proliferation and colony-forming ability were assessed. The expression level of cytoplasmic polyadenylation element binding protein 3 (CPEB3) was detected by real-time quantitative PCR and western blot. Lidocaine treatment resulted in decreased HepG2 cell viability and colony formation in a dose-dependent manner. In hepatocellular carcinoma patient samples, CPEB3 was downregulated and was associated with poor prognosis and high-grade malignancy. Additionally, CPEB3 was a critical mediator of lidocaine-induced repression of HepG2 cell proliferation. These results demonstrated that lidocaine decreased cell viability and colony-forming ability of HepG2 cells by upregulating CPEB3 expression.

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Chalcone-thiosemicarbazone Hybrids as Inhibitors of Human Hepatocellular Carcinoma HepG2 Cells Viability and Oxygen Consumption

Current Bioactive Compounds ◽

10.2174/1573407218666220111104011 ◽

2022 ◽

Vol 18 ◽

Author(s):

Vivian Cordeiro Rodrigues ◽

William Queiroz Felippe ◽

Carla Marins Goulart ◽

Aurea Echevarria ◽

Ana Paula Pereira da Silva

Keyword(s):

Hepatocellular Carcinoma ◽

Oxygen Consumption ◽

Cell Viability ◽

Hepg2 Cells ◽

Atp Synthesis ◽

Human Hepatocellular Carcinoma ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Open Chain

Background: Chalcones are open-chain flavonoids especially attractive to medicinal chemistry due to their easy synthesis and the possibility of structural modifications. Objective: Evaluate the in vitro anticancer activity of a series of hybrids chalcones-thiosemicarbazones against the human hepatocellular carcinoma cell line, HepG2. Methods: Seven hybrid chalcones-thiosemicarbazones (CTs), 3-(4’-X-phenyl)-1-phenylprop-2-en-1-one thiosemicarbazone, where X=H (CT-H), CH3 (CT-CH3), NO2 (CT-NO2), Cl (CT-Cl), CN (CT-CN), F (CT-F) and Br (CT-Br), were synthesized and their effects on cells viability and mitochondrial oxygen consumption were accessed. Results: Incubation with CTs caused a decrease in HepG2 cells viability in a time-concentration-dependent manner. The most effective compounds in inhibiting cell viability, after 24 hours of treatment, were CT-Cl and CT-CH3 (IC50 20.9 and 23.63 μM, respectively). In addition, using 10 M and only 1 hour of pre-incubation, CT-CH3 caused a reduction in basal respiration (-37%), oxygen consumption coupled with ATP synthesis (-60%) and maximum oxygen consumption (-54%). These alterations in respiratory parameters may be involved with the inhibitory effects of CT-CH3, since significant changes in oxygen consumption rates were observed in a condition that anticipates more significant losses of cell viability. The ADME parameters and the no violation of Lipinski Rule of Five showed that all compounds are safe. Conclusion: These results may contribute to the knowledge about the effects of CTs on these cells and the development of new treatments against HCCs.

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

10.21203/rs.3.rs-396990/v1 ◽

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

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:261-269 ◽

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.

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

Anesthesiology ◽

10.1097/aln.0000000000001528 ◽

2017 ◽

Vol 126 (5) ◽

pp. 868-881 ◽

Cited By ~ 36

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 < 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.

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Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

Current Bioactive Compounds ◽

10.2174/1573407214666181115124223 ◽

2020 ◽

Vol 16 (3) ◽

pp. 358-362

Author(s):

Renan S. Teixeira ◽

Paulo H.D. Carvalho ◽

Jair A.K. Aguiar ◽

Valquíria P. Medeiros ◽

Ademar A. Da Silva Filho ◽

...

Keyword(s):

Antitumor Activity ◽

Crude Extract ◽

Hepg2 Cells ◽

Liver Carcinoma ◽

Adhesion Assay ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Arctium Lappa ◽

Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

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The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis

Nutrients ◽

10.3390/nu13072178 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2178

Author(s):

Fabio Morandi ◽

Veronica Bensa ◽

Enzo Calarco ◽

Fabio Pastorino ◽

Patrizia Perri ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Viability ◽

Cell Cycle Progression ◽

Treatment Strategies ◽

Annexin V ◽

Dependent Manner ◽

Induction Of Apoptosis ◽

Dose Dependent

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.

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The Effect and Mechanism of Apoptosis Induced by Desacetylcinobufotalin (DEBF) in Human Hepatocellular Carcinoma HepG2 Cells

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.395-396.587 ◽

2013 ◽

Vol 395-396 ◽

pp. 587-590

Author(s):

Xu Chao ◽

Lin Dang ◽

Min Hui Wei

Keyword(s):

Hepatocellular Carcinoma ◽

Antitumor Activity ◽

Western Blot ◽

Hepg2 Cells ◽

Human Hepatocellular Carcinoma ◽

Inhibition Effect ◽

Marked Inhibition ◽

Mitochondria Pathway

The cytotoxicity of Desacetylcinobufotalin (DEBF) and apoptosis induced by DEBF was measured. Additionally the mechanism of Apoptosis induced by DEBF was studied through Western blot. The results show DEBF displayed the marked inhibition effect to HepG2 cells and the IC50value is 0.0279μmol/ml. The expression of Bax was significantly increased and the expression of Bcl-2 was markedly decreased, compared to the control. The data suggest DEBF had significant antitumor activity through induction apoptosis via mitochondria pathway.

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Synthesis, Characterization of Nano-β-Tricalcium Phosphate and the Inhibition on Hepatocellular Carcinoma Cells

Journal of Nanomaterials ◽

10.1155/2018/7083416 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Langlang Liu ◽

Yanzeng Wu ◽

Chao Xu ◽

Suchun Yu ◽

Xiaopei Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Particle Size ◽

Cell Viability ◽

Tricalcium Phosphate ◽

Hepg2 Cells ◽

Drug Carrier ◽

Average Particle Size ◽

Crystal Habit ◽

Average Particle ◽

Dependent Manner

It is difficult to synthesize nano-β-tricalcium phosphate (nano-β-TCP) owing to special crystal habit. The aim of this work was to synthesize nano-β-TCP using ethanol-water system and characterize it by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Malvern laser particle size analyzer, and transmission electron microscope (TEM). In addition, the inhibitory effect of nano-β-TCP on human hepatocellular carcinoma (HepG2) cells was also investigated using MTT assay, lactate dehydrogenase (LDH) leakage test, and 4′-6-diamidino-2-phenylindole (DAPI) staining. The results showed that negatively charged rod-like nano-β-TCP with about 55 nm in diameter and 120 nm in length was synthesized, and the average particle size of nano-β-TCP was 72.7 nm. The cell viability revealed that nano-β-TCP caused reduced cell viability of HepG2 cells in a time- and dose-dependent manner. These findings presented here may provide valuable reference data to guide the design of nano-β-TCP-based anticancer drug carrier and therapeutic systems in the future.

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Dihydroartemisinin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cell by Upregulating Tumor Necrosis Factor via JNK/NF-κB Pathways

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9581327 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Long Wu ◽

Yanlei Cheng ◽

Junjian Deng ◽

Weiping Tao ◽

Junjie Ye

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Differentially Expressed Genes ◽

Carcinoma Cell ◽

Expression Profiles ◽

Human Hepatocellular Carcinoma ◽

Differentially Expressed ◽

Venn Diagram ◽

Dependent Manner ◽

Hepatocellular Carcinoma Cell

Background. Dihydroartemisinin (DHA) is a predominant compound in Artemisia annua L., and it has been shown to inhibit tumorigenesis. Methods. In this study, the antitumor potential of DHA was investigated in the MHCC97-L hepatocellular carcinoma cell line. Cells were treated at various concentrations of DHA, and then the cell cycle, viability, and DNA synthesis were measured to evaluate cell proliferation. Furthermore, the expression of genes and proteins related to proliferation and apoptosis was measured to determine the effects of DHA. Finally, the mechanism was investigated using RNA-sequencing to identify differentially expressed genes and signaling pathways, and JNK/NF-κB pathways were evaluated with Western blotting. Results. Cells were treated with a concentration range of DHA from 1 to 100 μM, and cell proliferation was suppressed in a dose-dependent manner. In addition, the genes and proteins involved in typical cellular functions of MHCC97-L cells were significantly inhibited. DHA treatment downregulated the angiogenic gene ANGPTL2 and the cell proliferation genes CCND1, E2F1, PCNA, and BCL2. DHA treatment significantly upregulated the apoptotic genes CASP3, CASP8, CASP9, and TNF. Global gene expression profiles identified 2064 differentially expressed genes (DEGs). Among them, 744 were upregulated and 1320 were downregulated. Furthermore, MAPK, NF-kappa B, and TNF pathways were enriched based on the DEGs, and the consensus DEG was identified as TNF using a Venn diagram of those pathways. DHA promoted phosphorylation of JNK, inhibited nuclear p65, and then significantly induced TNF-α synthesis. Conclusion. DHA inhibited cell proliferation and induced apoptosis in human hepatocellular carcinoma cells by upregulating TNF expression via JNK/NF-κB pathways.

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