scholarly journals The mutational features of aristolochic acid-induced mouse and human liver cancers

2018 ◽  
Author(s):  
Zhao-Ning Lu ◽  
Qing Luo ◽  
Li-Nan Zhao ◽  
Yi Shi ◽  
Xian-Bin Su ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Human Liver ◽  
Aristolochic Acid ◽  
Human Cancer ◽  
Herbal Remedies ◽  
Dependent Manner ◽  
Genetic Event ◽  
Recurrent Mutations ◽  
Liver Cancers ◽  
Human Liver Cancer

AbstractAristolochic acid (AA) derived from traditional Chinese herbal remedies has recently been statistically associated with human liver cancer; however, the causal relationships between AA and liver cancer and the underlying evolutionary process of AA-mediated mutagenesis during tumorigenesis are obscure. Here, we subjected mice, including Pten-deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and carbon tetrachloride (CCl4), which may induce liver injury. Significantly, AAI promoted the development of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, in a dose-dependent manner, and it increased the incidence of liver cancer, together with CCl4 or Pten deficiency. AAI could lead to DNA damage and AAI-DNA adducts that initiate liver cancer via characteristic A>T transversions, as indicated by the comprehensive genomic analysis, which revealed recurrent mutations in Hras and some genes encoding components of the Ras/Raf, PI3K, Notch, Hippo, Wnt, DNA polymerase family and the SWI/SNF complex, some of which are also often found in human liver cancer. Mutational signature analysis across human cancer types revealed that the AA-related dominant signature was especially implicated in liver cancer in China, based on very stringent criteria derived from the animal cancer form, in which mutations of TP53 and JAK1 are prone to be significantly enriched. Interestingly, AAI-mediated characteristic A>T mutations were the earliest genetic event driving malignant subclonal evolution in mouse and human liver cancer. In general, this study provides documented evidence for AA-induced liver cancer with featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA-associated human cancers, especially liver cancer.

scholarly journals Inhibition of human liver cancer cell growth by evodiamine involves apoptosis and deactivation of PI3K/AKT pathway

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Jia Jia ◽  
Xigang Kang ◽  
Yanfang Liu ◽  
Jianwei Zhang
Keyword(s):  
Liver Cancer ◽  
Cancer Cell ◽  
Human Liver ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Liver Cancer Cell ◽  
Human Liver Cancer Cell ◽  
Human Liver Cancer ◽  
Induction Of Apoptosis

Abstract Evodiamine is an active alkaloid member found in Traditional Chinese Herb (TCH) Evodia rutaecarpa. It has been reported to exhibit remarkable biological and medicinal activities including anticancer and anti-inflammatory. This study was designed to investigate the anticancer effects of evodiamine against human liver cancer and evaluate its effects on cell migration, cell invasion, cellular apoptosis and PI3K/AKT pathway. The results showed that evodiamine exhibits potent antiproliferative effects against two human liver cancer cell lines (HepG2 and PLHC-1) with an IC50 of 20 µM. Nonetheless, the cytotoxic effects of evodiamine were comparatively low against the normal cells as evident from the IC50 of 100 μM. The growth inhibitory effects of evodiamine were found to be due to the induction of apoptosis as revealed by the DAPI, AO/EB and annexin V/PI staining assays. The induction of apoptosis was also associated with upregulation of Bax and downregulation of Bcl-2 expression in a concentration dependent manner. The wound healing and transwell assay revealed that evodiamine caused a significant decline in the migration and invasion of the HepG2 and PLHC-1 cells. Investigation of the effects of evodiamine on the PI3K/AKT signalling revealed that evodiamine inhibited the phosphorylation of PI3K and AKT proteins. Taken together, the results showed that evodiamine inhibits the growth of human liver cancer via induction of apoptosis and deactivation of PI3K/AKT pathway. The results point towards the therapeutic potential of evodiamine in the treatment of liver cancer.

scholarly journals The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3926
Author(s):  
Chen Chen ◽  
Qing Lv ◽  
Yang Li ◽  
Ying-Hua Jin
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Human Cancer ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.

scholarly journals A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Haojie Jin ◽  
Siying Wang ◽  
Esther A Zaal ◽  
Cun Wang ◽  
Haiqiu Wu ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Glutamine Metabolism ◽  
Chemical Library ◽  
Combination Strategy ◽  
Glutamine Transporter ◽  
Liver Cancers ◽  
Human Liver Cancer

The dependency of cancer cells on glutamine may be exploited therapeutically as a new strategy for treating cancers that lack druggable driver genes. Here we found that human liver cancer was dependent on extracellular glutamine. However, targeting glutamine addiction using the glutaminase inhibitor CB-839 as monotherapy had a very limited anticancer effect, even against the most glutamine addicted human liver cancer cells. Using a chemical library, we identified V-9302, a novel inhibitor of glutamine transporter ASCT2, as sensitizing glutamine dependent (GD) cells to CB-839 treatment. Mechanically, a combination of CB-839 and V-9302 depleted glutathione and induced reactive oxygen species (ROS), resulting in apoptosis of GD cells. Moreover, this combination also showed tumor inhibition in HCC xenograft mouse models in vivo. Our findings indicate that dual inhibition of glutamine metabolism by targeting both glutaminase and glutamine transporter ASCT2 represents a potential novel treatment strategy for glutamine addicted liver cancers.

Precise Electrical Detection of Curcumin Cytotoxicity in Human Liver Cancer Cells

2021 ◽  
Author(s):  
Novi Angeline ◽  
Sung-Sik Choo ◽  
Cheol-Hwi Kim ◽  
Suk Ho Bhang ◽  
Tae-Hyung Kim
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Electrical Detection ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

scholarly journals Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using Hepg2 Cell Line

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4593
Author(s):  
Deepthi Venkatachalapathy ◽  
Chandan Shivamallu ◽  
Shashanka Prasad ◽  
Gopenath Thangaraj Saradha ◽  
Parthiban Rudrapathy ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Vitis Vinifera ◽  
Bioactive Compounds ◽  
Camellia Sinensis ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Withania Somnifera ◽  
Antioxidant Properties ◽  
Annexin V ◽  
Human Liver Cancer

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

scholarly journals Aberrant miRNA expression response to UV irradiation in human liver cancer cells

2014 ◽  
Vol 9 (3) ◽  
pp. 904-910 ◽  
Author(s):  
GAOFENG LIANG ◽  
GUANGDA LI ◽  
YANYAN WANG ◽  
WANJUN LEI ◽  
ZHONGDANG XIAO
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Mirna Expression ◽  
Human Liver ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Expression Response ◽  
Human Liver Cancer Cells

MK2206 overcomes the resistance of human liver cancer stem cells to sorafenib by inhibition of pAkt and upregulation of pERK

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8047-8055 ◽  
Author(s):  
Beibei Zhai ◽  
Xiaofeng Zhang ◽  
Bin Sun ◽  
Lu Cao ◽  
Linlin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer

Growth Inhibitory Effects of IFN-βon Human Liver Cancer CellsIn VitroandIn Vivo

2007 ◽  
Vol 27 (6) ◽  
pp. 507-516 ◽  
Author(s):  
Sachiko Ogasawara ◽  
Hirohisa Yano ◽  
Seiya Momosaki ◽  
Jun Akiba ◽  
Naoyo Nishida ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Human Liver ◽  
Inhibitory Effects ◽  
Growth Inhibitory ◽  
Human Liver Cancer
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