scholarly journals Cistanche tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect through Combination with Cisplatin

2021 ◽  
Vol 20 ◽  
pp. 153473542110130
Author(s):  
Pengfei Yuan ◽  
Changshuang Fu ◽  
Yi Yang ◽  
Aipire Adila ◽  
Fangfang Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Effect ◽  
Matrix Metalloproteinase 2 ◽  
Phenylethanoid Glycosides ◽  
Antitumor Effects ◽  
Mapk Pathways ◽  
Cycle Arrest ◽  
Tumor Mouse Model ◽  
Cistanche Tubulosa ◽  
Endothelial Growth Factor

Cistanche tubulosa is a type of Chinese herbal medicine and exerts various biological functions. Previous studies have been demonstrated that Cistanche tubulosa phenylethanoid glycosides (CTPG) exhibit antitumor effects on a variety of tumor cells. However, the antitumor effects of CTPG on HepG2 and BEL-7404 hepatocellular carcinoma (HCC) cells are still elusive. Our study showed that CTPG significantly inhibited the growth of HepG2 and BEL-7404 cells through the induction of cell cycle arrest and apoptosis, which was associated with the activation of MAPK pathways characterized by the up-regulated phosphorylation of p38, JNK, and ERK1/2 and mitochondria-dependent pathway characterized by the reduction of mitochondrial membrane potential. The release of cytochrome c and the cleavage of caspase-3, -7, -9, and PARP were subsequently increased by CTPG treatment. Moreover, CTPG significantly suppressed the migration of HepG2 through reducing the levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Interestingly, CTPG not only enhanced the proliferation of splenocytes but also reduced the apoptosis of splenocytes induced by cisplatin. In H22 tumor mouse model, CTPG combined with cisplatin further inhibited the growth of H22 cells and reduced the side effects of cisplatin. Taken together, CTPG inhibited the growth of HCC through direct antitumor effect and indirect immunoenhancement effect, and improved the antitumor efficacy of cisplatin.

scholarly journals Cistanche Tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect Through Combination With Cisplatin

2021 ◽  
Author(s):  
Pengfei Yuan ◽  
Changshuang Fu ◽  
Yi Yang ◽  
Aipire Adila ◽  
Fangfang Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Effect ◽  
Matrix Metalloproteinase 2 ◽  
Vascular Endothelial ◽  
Phenylethanoid Glycosides ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Tumor Mouse Model ◽  
Cistanche Tubulosa ◽  
Endothelial Growth Factor

Abstract BackgroundPrevious studies have been demonstrated that Cistanche tubulosa phenylethanoid glycosides (CTPG) exhibit antitumor effects on a variety of tumor cells. However, the antitumor effects of CTPG on HepG2 and BEL-7404 hepatocellular carcinoma (HCC) cells are still elusive.ResultsOur study showed that CTPG significantly inhibited the growth of HepG2 and BEL-7404 cells through the induction of cell cycle arrest and apoptosis, which was associated with the activation of MAPK pathways characterized by the up-regulated phosphorylation of p38, JNK, and ERK1/2 and mitochondria-dependent pathway characterized by the reduction of mitochondrial membrane potential. The release of cytochrome c and the cleavage of caspase-3, -7, -9 and PARP were subsequently increased by CTPG treatment. Moreover, CTPG significantly suppressed the migration of HepG2 through reducing the levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Interestingly, CTPG not only enhanced the proliferation of splenocytes but also reduced the apoptosis of splenocytes induced by cisplatin. In H22 tumor mouse model, CTPG combined with cisplatin further inhibited the growth of H22 cells and reduced the side effects of cisplatin.ConclusionTaken together, CTPG inhibited the growth of HCC through direct antitumor effect and indirect immunoenhancement effect, improved the antitumor efficacy of cisplatin.

scholarly journals miR-100 Suppresses the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma Cells via Targeting CXCR7

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yiman Ge ◽  
Jia Shu ◽  
Gang Shi ◽  
Fuguo Yan ◽  
Yejing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Antitumor Effects ◽  
Hepatocellular Carcinoma Cells ◽  
Invasion And Migration ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Endothelial Growth Factor

This study is to elucidate the functions of miR-100 in hepatocellular carcinoma progression and to explore the underlying mechanisms. Expression levels of miR-100 in normal-cancer hepatocellular carcinoma tissues were measured using quantitative real-time PCR (qRT-PCR). The invasive and proliferative abilities of hepatocellular carcinoma cell lines transfected with mimic-NC or mimic-miR-100 were measured using transwell, CCK-8, and colony formation assays. The binding sites between CXCR7 and miR-100 were determined using luciferase reporter assays. The correlation of CXCR7 and miR-100 in hepatocellular carcinoma progression was further confirmed by cotransfection assays. Our results showed that miR-100 was significantly lower expressed in hepatocellular carcinoma tissues and negatively associated with CXCR7 expression. Cell functional assays’ results found that upregulation of miR-100 inhibited the proliferative, invasive, and migrative abilities in hepatocellular carcinoma cells. Luciferase reporter assay suggested that CXCR7 mRNA and miR-100 bound one another. Increasing CXCR7 expression reversed the inhibitive effects of upregulated miR-100 in hepatocellular carcinoma cells. Further study showed that miR-100/CXCR7 played a role in hepatocellular carcinoma progression by regulating metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF). Conclusively, miR-100 exerts antitumor effects on hepatocellular carcinoma. Overexpression of miR-100 attenuates the invasive and proliferative abilities of hepatocellular carcinoma cells by targeting CXCR7.

scholarly journals The Ethanolic Extract ofTaiwanofungus camphoratus(Antrodia camphorata) Induces Cell Cycle Arrest and Enhances Cytotoxicity of Cisplatin and Doxorubicin on Human Hepatocellular Carcinoma Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Liang-Tzung Lin ◽  
Chen-Jei Tai ◽  
Ching-Hua Su ◽  
Fang-Mo Chang ◽  
Chen-Yen Choong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Ethanolic Extract ◽  
Carcinoma Cells ◽  
Antrodia Camphorata ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Chemotherapy Agents ◽  
Human Hepatocellular Carcinoma Cells

Taiwanofungus camphoratus(synonymAntrodia camphorata) is a widely used medicinal fungus in the folk medicine of Taiwan with several pharmacological features such as anti-inflammatory, liver protection, antihypertensive, and antioxidative activities. The ethanolic extract ofT. camphoratus(TCEE) which contains abundant bioactive compounds including triterpenoids and polysaccharides also has antitumor effects in various human cancer cell lines. The aims of this study are to clarify the antitumor effects of TCEE on human hepatocellular carcinoma cells and also evaluate the combination drug effects with conventional chemotherapy agents, cisplatin and doxorubicin. In the present study, the TCEE treatment induced cell cycle arrest and suppressed cell growth on both Hep3B and HepJ5 cells. Expression of cell cycle inhibitors, P21 and P27, and activation of apoptosis executer enzyme, caspase-3, were also induced by TCEE. In combination with the chemotherapy agents, TCEE treatment further enhanced the tumor suppression efficiency of cisplatin and doxorubicin. These results together suggested that TCEE is a potential ingredient for developing an integrated chemotherapy for human liver cancer.

scholarly journals Combined Therapy with Dendritic Cell Loaded-Exosomes Supplemented with PD-1 Inhibition Have Superior Antitumor Effect in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Shengbin Shi ◽  
Cuijuan Wang ◽  
Chuangnian Zhang ◽  
Wenyu Zhang ◽  
Yibo Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd8 T Cells ◽  
Antitumor Effect ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Antitumor Effects ◽  
Time Points

Abstract Background Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths and has low sensitivity to conventional therapies. Dendritic cell (DC) loaded tumor-exosomes (TEX) have shown antitumor effects in a murine HCC model. However, the combined antitumor efftcts of DC-TEX and programmed death protein 1 antibody (PD-1 Ab) at different time application has not been investigated. Methods In this study, ectopic, orthotopic, and diethylnitrosamine (DENA)-induced HCC models were established and treated with DC-TEX alone or in combination with PD-1 Ab at different time points. Meanwhile, we established an orthotopic HCC model in BALB/C nude mice and restore t cells. Results The results showed that along with the increased number of CD8+ T cells, the PD-1+CD8+ T-cell population was also significantly increased after DC-TEX injection. The number of CD8+ T cells peaked 72 h after DC-TEX injection, and the PD-1+CD8+ T cells also showed a similar result. Subsequently, the PD-1 Ab was applied in combination with DC-TEX at a series of time points (0, 24,72, 96, 120 or 168 h). Surprisingly, the combined treatment showed strong antitumor effects and this effect was most prominent when PD-1 Ab was administerd at 72 h. In vitro, PD-1 Ab also significantly reversed the proliferative ability of PD-1+CD8+ T cells at 72 h. The combined antitumor effects of PD-1 Ab and DC-TEX were mainly through their stimulation on CD8+T cells proliferation as well as repression for T cell exhaustion. Conclusion In conclusion, the combination of DC-TEX and PD-1 Ab significantly suppresses tumor growth in a murine HCC model and that the antitumor effect is affected by the timing of PD-1 Ab treatment.

L-Tetrahydropalmatine Inhibits the Progression of Glioblastoma Tumor by Suppressing the Extracellular-Signal-Regulated Kinase/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 164-171
Author(s):  
Feng Xue ◽  
Tingting Chen
Keyword(s):  
Glioblastoma Multiforme ◽  
Nuclear Factor Kappa B ◽  
Matrix Metalloproteinase 2 ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Extracellular Signal ◽  
Apoptosis Protein ◽  
Endothelial Growth Factor

Glioblastoma multiforme is the most common malignancy of central nervous system. Herein we have evaluated the effect of L-tetrahydropalmatine, an isoquinoline alkaloid, on the tumor growth both in vivo and in vitro using C6 glioblastoma multiforme cells and BALB/c mice injected subcutaneously with C6/luc2 cells. The results of these studies show that L-tetrahydropalmatine exhibited cytotoxic effect on C6 glioblastoma multiforme cells, suppressed nuclear factor-kappa B activity, suppressed the levels of tumor-linked proteins such as matrix metalloproteinase-2/9, Cyclin-D1, vascular endothelial growth factor, and X-linked inhibitor of apoptosis protein via ERK/nuclear factor-kappa B cascade. Further, L-tetrahydropalmatine inhibited the cell migration and invasion properties of C6 cells, and also suppressed the tumor weight and volume in mice. Immunohistochemical staining of tumor tissues suggested that L-tetrahydropalmatine inhibited the extracellular-signal-regulated kinase/nuclear factor-kappa B cascade and suppressed the levels of Cyclin-D1; matrix metalloproteinase-2/9; X-linked inhibitor of apoptosis protein; and vascular endothelial growth factor, and also the progression and growth of glioblastoma multiforme in mice. In summary, L-tetrahydropalmatine inhibits the ERK/nuclear factor-kappa B cascade, decreases the tumor volume, and inhibits the proteins responsible for tumor growth both in vivo and in vitro.

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