Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342+ /PI+ dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3. Moreover, JS-K-treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C), decrease of anti-apoptotic Bcl-2 family-protein expression including p-Bcl-2 (Ser70), Bcl-2, Bcl-xL, and Mcl-1 as well as the increase of pro-apoptosis Bcl-2 family-protein including Bim, Bad, Bax, and Bak. Furthermore, JS-K caused a marked increase of intracellular NO levels while pre-treatment with Carboxy-PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre-treatment with Carboxy-PTIO attenuated the JS-K-induced up-regulation of PP2A, Cyt c, and cleaved-caspase-9/3 activation. The silencing PP2A-C by siRNA could abolish the activation of PP2A-C, down-regulation of anti-apoptotic Bcl-2 family-protein (p-Bcl-2, Bcl-2, Bcl-xL, and Mcl-1), increase of pro-apoptosis Bcl-2 family-protein (Bim, Bad, Bax, and Bak) and apoptotic-related protein (Cyt c, cleaved caspase-9/3) that were caused by JS-K in HepG2 cells. In addition, pre-treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS-K. In summary, NO release from JS-K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl-2 family proteins.
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PMID:Protein phosphatase 2A mediates JS-K-induced apoptosis by affecting Bcl-2 family proteins in human hepatocellular carcinoma HepG2 cells. 2969 50

Inonotus baumii, a traditional medicinal mushroom, has been historically used in China and other countries of East Asia for the treatment of various diseases. The aim of this study is to investigate the antitumor activity of the extract of I. baumii (EIB) against hepatocellular carcinoma and the possible mechanism involved. The MTT assay was used to evaluate the proliferative activity of SMMC-7721 cells treated with EIB. Hoechst 33258 and JC-1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. Flow cytometry analysis indicated that EIB blocked the cell cycle at the S phase and induced significant apoptosis. EIB increased the protein expression of Bax, cytochrome c, cleaved caspase-3, and decreased Bcl-2 in SMMC-7721. Moreover, EIB induced autophagy, indicated by the increase of autophagy-related protein expression of LC3-II and decrease of p62, and the AMPK/mTOR/ULK1 pathway was involved in the autophagic cell death. In vivo, EIB was found to strongly inhibit the growth of tumors in BALB/c nude mice. Our results indicated that I. baumii might be a potential natural therapeutic agent for liver cancer, as it could induce apoptosis and autophagy in HCC cells.
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PMID:The Antitumor Potential of Extract of the Oak Bracket Medicinal Mushroom Inonotus baumii in SMMC-7721 Tumor Cells. 3166 69

Hypoxia, as a form of stress, plays a critical role in oncogenesis, including metabolic reprogramming. Mitochondrial, the centers of energy production, re-balance mitochondria dynamic to maintain cell survival during high levels of environmental stresses. NDRG1 is a hypoxia-inducible protein that is involved in various human cancers, including HCC. However, little is known about whether NDRG1 participants in the quality control of mitochondrial in times of stress. Here, we firstly showed that how NDRG1 exerted its role through mediating mitochondrial dynamic in HCC cells under hypoxia. Initially, we identified that NDRG1 expression varies with oxygen content. NDRG1 silencing notably induced cell apoptosis under hypoxia, while no obviously change of wildtype cells in hypoxia compared with that in normoxia. Further analysis revealed that NDRG1 silencing in HCC cells led to increase of pro apoptotic protein BAX and decrease in anti-apoptotic proteins Bcl-2 and Bclx, which meant mitochondrial damage were induced. In the analysis of mitochondria, we found that more released cytochrome c located in cytosolic with NDRG1 knockdown in hypoxia, which may be due to mitochondria division. And the following experiment proved that more fragmented mitochondria were presented in NDRG1 silencing cells, as well as destroyed mitochondrial membrane potential with evidence by JC-1 was verified. Moreover, these trends could be reversed by Mdivi1. Further research showed that NDRG1 silencing disrupt hypoxia-enhanced aerobic glycolysis through effectively decreased glucose uptake, lactate output and ECAR value. In sum, we provide the first direct evidence that NDRG1-driven change in mitochondrial dynamics and aerobic glycolysis maintain cells survival in HCC during hypoxia.
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PMID:Hypoxia-induced elevated NDRG1 mediates apoptosis through reprograming mitochondrial fission in HCC. 3216 97

The edible mushroom Grifola frondosa has been used as a functional food for diseases prevention and therapy in Asian countries. In the present work, an acid-soluble polysaccharide (GFAP) was prepared from Grifola frondosa under room temperature and hydrochloric acid solution treatment, and its inhibitory effects on H22 and HepG2 cells were investigated. Results of MTT indicated that GFAP could effectively suppress proliferations of HCC cells, dose-dependently. Microscopic observation results demonstrated that GFAP-treated HCC cells showed apoptotic characteristics like membrane blebbing, chromatin condensed, nucleus pycnosis and fragmentation. Annexin V-FITC/PI staining and cell cycle distribution results showed that GFAP could induce the apoptosis of H22 and HepG2 cells via arresting them in G1 and S phases respectively. Rh123, JC-1 staining and western blotting results suggested that GFAP could significantly increase the permeability of mitochondrial membrane of HCC cells, and upregulated the expressions of Bax, cytochrome c, cleaved-caspase-3 and cleaved-caspase-9, which indicated that GFAP could trigger apoptosis of HCC cells through mitochondria apoptotic pathway in a caspases-dependent pattern. Our data demonstrated that GFAP holds great application prospect as a safe and effective antitumor drug for hepatocellular carcinoma therapy.
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PMID:The caspases-dependent apoptosis of hepatoma cells induced by an acid-soluble polysaccharide from Grifola frondosa. 3242 65

Raptinal is a novel antineoplastic agent that induces an expeditious intrinsic apoptotic pathway, in addition to the shutdown of mitochondrial function for cancerous cells, because of silver nanoparticles (AgNPs) that have been shown to provide a worthy approach to overcome tumors. In this study, Both Raptinal and Raptinal-loaded silver nanoparticles (AgNPs) were tested as the first time in hepatocellular carcinoma-induced mice to evaluate its efficacy and targeting to HCC. Seventy-two albino male mice of comparable age were classified into six groups; early stage of HCC was induced using diethyl nitrosamine (DEN)/carbon tetrachloride (CCL4). Liver function was assessed in all groups using ALT, AST, total bilirubin, and alpha-fetoprotein (AFP) as well as histopathological examination. Quantitative gene expression of key apoptotic gene markers p53, cytochrome c, and caspase 3 was assessed in all liver homogenates. The results showed that Raptinal-loaded AgNPs group had significant increase in both apoptotic genes of cytochrome c and Caspase 3 at P = 0.0001 compared with Raptinal-free drug group. AFP levels were significantly decreased in Raptinal-loaded AgNPs group compared with both Raptinal-free drug and HCC groups at P = 0.0001. Degenerative changes in the hepatocytes with focal necrosis and inflammatory cell infiltration in histopathology confirm the biochemical analysis. Our study is considered one of the first studies using Raptinal in vivo. Moreover, it showed that Raptinal and/or the combination between Raptinal and AgNPs showed a promising therapeutic agent in treating early HCC.
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PMID:Raptinal silver nanoparticles: new therapeutic advances in hepatocellular carcinoma mouse model. 3294 92


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