scholarly journals Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTEN-FOXO4 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
An-Ting Liou ◽  
Mei-Fang Chen ◽  
Chu-Wen Yang
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Hepatoma Cell ◽  
Hep3b Cell ◽  
Hepatoma Cell Line ◽  
Potential Candidate ◽  
Curcumin Treatment ◽  
Liver Cancers ◽  
Hep3b Cells

Objective. Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. Results. AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment. Overexpression of FOXO4 increases the sensitivity of Hep3B cells to curcumin. Knockdown of the FOXO4 gene by siRNA inhibits the proapoptotic effects of curcumin on Hep3B cell. Conclusions. This study revealed the AKT/PTEN/FOXO4 pathway as a potential candidate of target for treatment of p53-null liver cancers.

scholarly journals Chemical Constituents From the Fruits of Xanthium strumarium and Their Antitumor Effects

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094554
Author(s):  
Chao Tong ◽  
Ri-Hui Chen ◽  
Ding-Cheng Liu ◽  
De-Sheng Zeng ◽  
Hui Liu
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Hepatoma Cell ◽  
Cancer Cell Line ◽  
Xanthium Strumarium ◽  
Hepatoma Cell Line ◽  
Human Gastric Cancer ◽  
Antitumor Effects ◽  
Mcf 7

A new neolignan, (7 S,8 R)- threo-1′-[3′-hydroxy-7-(4-hydroxy-3,5-dimethoxyphenyl)-8-hydroxymethyl-7,8-dihydrobenzofuran]acrylaldehyde (1), along with 5 known compounds 2-6, were isolated from the fruits of Xanthium strumarium. Their structures were elucidated by extensive spectroscopic methods. All the isolates were evaluated for in vitro cytotoxicity against human cancer cell lines, including human hepatoma cell line (HepG2), human breast cancer cell line (MCF-7), human colon cancer cell line (HCT-116), and human gastric cancer cell line (SGC-7901). Among them, compounds 1 and 3 showed selective cytotoxicity on HepG2 cancer cells with half-maximal inhibitory concentration (IC50) values of 10.2 ± 1.2 and 18.3 ± 1.6 μM, respectively. Moreover, compound 5 also exhibited moderate cytotoxicity against MCF-7 cancer cells with an IC50 value of 20.5 ± 1.3 μM.

scholarly journals Effects of cyclosporin A on erythropoietin production by the human Hep3B hepatoma cell line

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 978-984
Author(s):  
AM Vannucchi ◽  
A Grossi ◽  
A Bosi ◽  
D Rafanelli ◽  
M Statello ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Cell Line ◽  
Secretory Pathway ◽  
Hepatoma Cell ◽  
Allogeneic Bone Marrow Transplantation ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Allogeneic Bone ◽  
Hep3b Cells

There is evidence that the inadequate erythropoietin (Epo) production observed in patients undergoing allogeneic bone marrow transplantation (BMT) might be ascribed to an inhibitory effect caused by the immunosuppressive drug cyclosporin A (CsA). In this in vitro study, we have evaluated the effects of CsA on the release of Epo in the culture medium by the human Hep3B hepatoma cell line. In cultures incubated with both CsA and the nonimmunosuppressive CsA analog MeAla-6, but not with the CsA-unrelated immunosuppressive agent FK-506, the levels of Epo in the medium were significantly reduced in comparison with controls, at concentrations (0.01 to 1.6 mumol/L) not affecting total protein synthetic rate nor the constitutive secretion of alpha- fetoprotein. Hep3B cells were found to contain a CsA-binding molecule, with an M(r) of 18 Kd, as assessed by high performance liquid chromatography (HPLC) and ligand-blotting analysis. CsA did not affect the expression of the Epo gene, as judged by Northern blot analysis, but caused a significant amount of Epo to remain unsecreted within the cells; almost all (97% of total) of the intracellular Epo was associated with the plasma membrane subcellular fraction. We conclude that: (1) CsA is able to inhibit Epo release in vitro by Hep3B cells, further supporting the hypothesis that the drug might have a role in the inappropriately low Epo levels observed in BMT patients; (2) the inhibitory effect appears to be specific and not caused by a general impairment of protein synthesis and/or secretion; and (3) the reduced Epo levels found in the medium of CsA-treated Hep3B cultures are supposed to be the consequence of an inability of the cells to correctly process Epo molecules for the secretory pathway.

scholarly journals Effects of cyclosporin A on erythropoietin production by the human Hep3B hepatoma cell line

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 978-984 ◽  
Author(s):  
AM Vannucchi ◽  
A Grossi ◽  
A Bosi ◽  
D Rafanelli ◽  
M Statello ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Cell Line ◽  
Secretory Pathway ◽  
Hepatoma Cell ◽  
Allogeneic Bone Marrow Transplantation ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Allogeneic Bone ◽  
Hep3b Cells

Abstract There is evidence that the inadequate erythropoietin (Epo) production observed in patients undergoing allogeneic bone marrow transplantation (BMT) might be ascribed to an inhibitory effect caused by the immunosuppressive drug cyclosporin A (CsA). In this in vitro study, we have evaluated the effects of CsA on the release of Epo in the culture medium by the human Hep3B hepatoma cell line. In cultures incubated with both CsA and the nonimmunosuppressive CsA analog MeAla-6, but not with the CsA-unrelated immunosuppressive agent FK-506, the levels of Epo in the medium were significantly reduced in comparison with controls, at concentrations (0.01 to 1.6 mumol/L) not affecting total protein synthetic rate nor the constitutive secretion of alpha- fetoprotein. Hep3B cells were found to contain a CsA-binding molecule, with an M(r) of 18 Kd, as assessed by high performance liquid chromatography (HPLC) and ligand-blotting analysis. CsA did not affect the expression of the Epo gene, as judged by Northern blot analysis, but caused a significant amount of Epo to remain unsecreted within the cells; almost all (97% of total) of the intracellular Epo was associated with the plasma membrane subcellular fraction. We conclude that: (1) CsA is able to inhibit Epo release in vitro by Hep3B cells, further supporting the hypothesis that the drug might have a role in the inappropriately low Epo levels observed in BMT patients; (2) the inhibitory effect appears to be specific and not caused by a general impairment of protein synthesis and/or secretion; and (3) the reduced Epo levels found in the medium of CsA-treated Hep3B cultures are supposed to be the consequence of an inability of the cells to correctly process Epo molecules for the secretory pathway.

Solena amplexicaulis Induces Cell Cycle Arrest, Apoptosis and Inhibits Angiogenesis in Hepatocarcinoma Cells and HUVECs

2014 ◽  
Vol 42 (06) ◽  
pp. 1521-1537 ◽  
Author(s):  
Jie Ren ◽  
Yuan Yuan Xu ◽  
He Fei Jiang ◽  
Meng Yang ◽  
Qian Hui Huang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Endothelial Cell Migration ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Solena Amplexicaulis ◽  
Protein Expressions

Solena amplexicaulis (Lam.) Gandhi (SA) has been used as a traditional medicine for the treatment of dysentery, multiple abscess, gastralgia, urethritis, and eczema in the minority area of China. This study was aimed to examine the cell proliferation inhibitory activity of the SA extract (SACE) and its mechanism of action in human hepatoma cell line (HepG2) and evaluate its anti-angiogenesis activity in human umbilical vein endothelial cell line (HUVEC). SACE could inhibit the growth of HepG2 cells in a dose- and time-dependent manner. FCM analysis showed that SACE could induce G2/M phase arrest, cell apoptosis, the mitochondrial membrane potential loss (ΔΨm) and increase the production of intracellular ROS of HepG2 cells. After treatment with SACE, topical morphological changes of apoptotic body formation, obvious increase of apoptosis-related protein expressions, such as Bax, cytochrome c, caspase-3, PARP-1, and decrease of Bcl-2, procaspase-9 protein expressions were observed at the same time. Moreover, SACE caused the significant inhibition of endothelial cell migration and tube formation in HUVEC cells. The results suggested that SACE could act as an angiogenesis inhibitor and induce cell apoptosis via a caspase-dependent mitochondrial pathway. Therefore, SACE could be a potent candidate for the prevention and treatment of liver cancer.

scholarly journals mTORC1 inhibition increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON

2011 ◽  
Vol 301 (1) ◽  
pp. C213-C226 ◽  
Author(s):  
Jing Li ◽  
Jianyu Liu ◽  
Jun Song ◽  
Xiaofu Wang ◽  
Heidi L. Weiss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Endocrine Cell ◽  
Promoter Activity ◽  
Hepatoma Cell ◽  
Mitogen Activated Protein Kinase ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Hep3b Cells ◽  
Bon Cells

The mammalian target of rapamycin (mTOR) signaling exists in two complexes: mTORC1 and mTORC2. Neurotensin (NT), an intestinal hormone secreted by enteroendocrine (N) cells in the small bowel, has important physiological effects in the gastrointestinal tract. The human endocrine cell line BON abundantly expresses the NT gene and synthesizes and secretes NT in a manner analogous to that of N cells. Here, we demonstrate that the inhibition of mTORC1 by rapamycin (mTORC1 inhibitor), torin1 (both mTORC1 and mTORC2 inhibitor) or short hairpin RNA-mediated knockdown of mTOR, regulatory associated protein of mTOR (RAPTOR), and p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells. c-Jun activity was increased by rapamycin or torin1 or p70S6K knockdown. c-Jun overexpression dramatically increased NT promoter activity, which was blocked by PD98059, an mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, overexpression of MEK1 or extracellular signal-regulated kinase 1 (ERK1) increased c-Jun expression and NT promoter activity. More importantly, PD98059 blocked rapamycin- or torin1-enhanced NT secretion. Consistently, rapamycin and torin1 also increased NT gene expression in Hep3B cells, a human hepatoma cell line that, similar to BON, expresses high levels of NT. Phosphorylation of c-Jun and ERK1/2 was also increased by rapamycin and torin1 in Hep3B cells. Finally, we showed activation of mTOR in BON cells treated with amino acids, high glucose, or serum and, concurrently, the attenuation of ERK1/2 and c-Jun phosphorylation and NT secretion. Together, mTORC1, as a nutrient sensor, negatively regulates NT secretion via the MEK/ERK/c-Jun signaling pathway. Our results identify a physiological link between mTORC1 and MEK/ERK signaling in controlling intestinal hormone gene expression and secretion.

scholarly journals SWCNH (Single walled carbon nanohorn) supervises ER (Endoplasmic reticulum) stress through triggering autophagy process of hepatocytes, especially in hepatoma cell line HepG2

2021 ◽  
Author(s):  
Jinling Dong ◽  
Ying Zhang ◽  
Zhihong Xie ◽  
Jie He ◽  
Tiantian Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blot ◽  
Er Stress ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Catabolic Pathway ◽  
Hepatoma Cell Line Hepg2

Abstract Backgrounds: The cellular homeostasis is major maintained by the catabolic pathway of autophagy. Our previous work indicated that SWCNH were associated with endoplasmic reticulum (ER) stress mediated by calcium flow and autophagic response. But, its mechanism was unclear. Methods: The regulation of SWCNH on the calcium flow then autophagy of liver cells were investigated through inducing ER stress with tunicamycin and SWCNH. The calcuim flow was determined using Fluo-3, then autophagy was examined with immunofluorescence or western blot for LC3, Beclin-1, ATG-5, and p62. Moreover, the apopototic protein of Bax and Bcl-2 was detected, too. Results: Tunicamycin-induced ER stress in hepatocytes was related to calcium flow, especially for hepatoma cell line HepG2. Moreover, SWCNH participated in the regulation of endoplasmic reticulum stress-related calcium flow. Besides, SWCNH induced hepatocyte autophagy and inhibited cell apoptosis, then mediated the process of hepatocyte autophagy. Conclusions: Tunicamycin-induced ER stress in hepatocytes was related to calcium flow. Moreover, SWCNH induced hepatocyte autophagy, inhibited cell apoptosis, and participated in the autophagy regulation of hepatocyte, especially for hepatoma cell line.

Endothelial Cell Protein S Synthesis Is Upregulated by the Complex of IL-6 and Soluble IL-6 Receptor

1997 ◽  
Vol 77 (05) ◽  
pp. 1014-1019 ◽  
Author(s):  
W Craig Hooper ◽  
Donald J Phillips ◽  
Bruce L Evatt
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Hepatoma Cell ◽  
Protein S ◽  
Oncostatin M ◽  
Cell Protein ◽  
Microvascular Endothelial Cell ◽  
Hepatoma Cell Line

SummaryWe have recently demonstrated that the proinflammatory cytokine, interleukin-6 (IL-6), could upregulate the production of protein S in the human hepatoma cell line, HepG-2, but not in endothelial cells. In this study, we have demonstrated that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could significantly upregulate protein S production in both primary human umbilical vein endothelial cells (HUVEC) and in the immortalized human microvascular endothelial cell line, HMEC-1. The IL-6/sIL-6R complex was also able to rapidly induce tyrosine phosphorylation of the IL-6 transducer, gpl30. Neutralizing antibodies directed against either IL-6 or gpl30 blocked protein S upregulation by the IL-6/sIL-6R complex. It was also observed that exogenous sIL-6R could also upregulate protein S by forming a complex with IL-6 constitutively produced by the endothelial cell. Two other cytokines which also utilize the gpl30 receptor, oncostatin M (OSM) and leukemia inhibitory factor (LIF), were also able to upregulate endothelial cell protein S. This study demonstrates a mechanism that allows endothelial cells to respond to IL-6 and also illustrates the potential importance of circulating soluble receptors in the regulation of the anticoagulation pathway.

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