Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A weblogo has been generated from the sequences surrounding 433 Ser/Thr protein residues whose phosphorylation by protein kinase CK2 had been previously validated ("bona fide" CK2 phosphosites). This has been compared to the weblogo extracted from 2275 putative CK2 phosphosites displaying the motif pS/pT-x1-x2-D/E/pS (where x1 not=P) present in the human phosphoElm database including 10899 naturally occurring phosphosites. The two weblogos are strikingly similar supporting the notion that indeed the 2275 putative sites (accounting for 20.9% of the whole phosphoproteome they belong to), or at least the great majority of these are generated by CK2. This conclusion has been corroborated by the random validation of 8 of such putative CK2 sites (belonging to 5 different proteins) as real targets of CK2 in vitro and/or in cells, leading to the inclusion into the repertoire of bona fide CK2 targets of 5 new entries, namely: oxidative stress-responsive kinase-1, anthrax toxin receptor 1, hepatoma derived growth factor, EpsinR and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like.
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PMID:Extraordinary pleiotropy of protein kinase CK2 revealed by weblogo phosphoproteome analysis. 1933 13

During the search of new anti-cancer agent from high fungi, the ethyl acetate extract of the mushroom Suillus placidus was found to exhibit a significant cytotoxic activity against human hepatoma HepG2 cells. With bioassay-guided fractionation, a cytotoxic component suillin was isolated from the extract. The anti-cancer effect of suillin was subsequently examined in 8 human cancer cell lines by using MTT assay. It is of interest to note that human liver cancer cells (HepG2 cells, Hep3B cells, and SK-Hep-1) were preferentially killed by suillin with an IC(50) of approximately 2microM in a 48h treatment. Mechanistically. suillin was found for the first time to induce apoptosis in HepG2 cells as characterized by DNA fragmentation, phosphatidyl-serine (PS) externalization, activation of caspase-3, -8, -9, depolarization of mitochondrial membrane potential, as well as release of cytochrome c into the cytosol. Moreover, the apoptosis induced by suillin was suppressed by both caspase-8 and -9 inhibitors. Western blot analysis revealed significant increases in the protein levels of Fas death receptor, adaptor FADD protein, pro-apoptotic protein Bad and a decline of Bid. These results suggest that the induction of apoptosis by suillin is through both death receptor and mitochondrial pathways. Taken together, our results suggest that suillin might be an effective agent to treat liver cancer.
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PMID:Suillin from the mushroom Suillus placidus as potent apoptosis inducer in human hepatoma HepG2 cells. 1961 21

The purpose of this study is to investigate in vitro and ex vivo effects of matrine on the growth of human lung cancer and hepatoma cells and the cancer cell migration as well as the expressions of related proteins in the cancer cells. Matrine significantly inhibited the in vitro and ex vivo growth of human non-small cell lung cancer A549 and hepatoma SMMC-7721 cells. Matrine induced the apoptosis in A549 and SMMC-7721 cells. Western blot analysis indicated that matrine dose-dependently down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein bax, eventually leading the reduction of ratios of Bcl-2/Bax proteins in A549 and SMMC-7721 cells. Furthermore, matrine significantly suppressed the A549 cell migration without reducing the cell viability. In addition, matrine dramatically reduced the secretion of vascular endothelial growth factor A in A549 cells. More importantly, matrine markedly enhanced the anticancer activity of anticancer agent trichostatin A (the histone deacetylase inhibitor) by strongly reducing the viability and/or the ratio of Bcl-2/Bax protein in A549 cells. Our findings suggest that matrine may have the broad therapeutic and/or adjuvant therapeutic application in the treatment of human non-small cell lung cancer and hepatoma.
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PMID:Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. 1964 19

Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG(2), and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF-kappaB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-kappaB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells.
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PMID:p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells. 2035 Jul 81

1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane (DP), a novel synthesized 1,3-diarylpropanes compound, showed growth inhibitory effect on human hepatoma HepG2 cells in a concentration-dependent manner. The growth inhibitory effect of DP on HepG2 cells was associated with microtubule depolymerization, G2/M phase arrest and apoptosis induction. The G2/M phase arrest induced by DP resulted from its microtubule-depolymerizing ability, and DP-treated HepG2 cells finally underwent caspase-dependent apoptosis. DP increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and pro-apoptotic protein Bax, but decreased the levels of anti-apoptotic protein Bcl-2. Meanwhile, the decrease in the mitochondrial membrane potential (MMP) and the release of cytochrome c from mitochondria were observed in DP-treated HepG2 cells. DP increased the levels of reactive oxygen species (ROS) in HepG2 cells, and antioxidant N-acetylcysteine (NAC) completely blocked DP-induced ROS accumulation and the disruption of the balance between Bax and Bcl-2 proteins, and effectively blocked the decreased MMP and apoptosis, but had no effect on the activation of caspase-8 and the up-regulations of DR4 and DR5 induced by DP. These results suggest that DP induces G2/M phase arrest through interruption of microtubule network followed by the death receptor- and ROS-mediated apoptosis in HepG2 cells.
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PMID:1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane with microtubule-depolymerizing ability induces G2/M phase arrest and apoptosis in HepG2 cells. 2067 58

This study aims to investigate apoptosis induced by lexatumumab (Lexa) in hepatocellular carcinoma (HCC) cells. We assessed the sensitivity of HCC cell lines and normal human hepatocytes to Lexa and explored the sensitization of HCC cells to Lexa-induced apoptosis by cycloheximide (CHX). Our data indicated that CHX sensitized HCC cell lines to Lexa-induced apoptosis, whereas treatment using solely CHX or Lexa was ineffective. The sequential treatment of CHX followed by Lexa dramatically induced caspase-dependent apoptosis in HCC cells and had synergistically increased intracellular rates of reactive oxygen species (ROS). Additionally, when ROS production was blocked by N-acetyl-L-cysteine (NAC), HCC cells were protected against Lexa and CHX combination treatment-induced apoptosis. ROS generation induced by combination treatment of Lexa and CHX triggered pro-apoptotic protein Bax oligomerization, conformation change, and translocation to mitochondria, which resulted in the release of cytochrome c and subsequent cell death. Furthermore, HSP90 was involved in mediating Lexa and CHX combination treatment-induced ROS increase and apoptotic death. More importantly, we observed that combination treatment of Lexa and CHX did not cause apoptotic toxicity in normal human primary hepatocytes. These results suggest that Lexa and CHX combination treatment merits investigation for the development of therapies for patients with HCC.
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PMID:Reactive oxygen species is essential for cycloheximide to sensitize lexatumumab-induced apoptosis in hepatocellular carcinoma cells. 2134 35

Hepatocellular carcinoma (HCC) constitutes a predominant part of primary liver cancer which ranks as the fifth most common cancer as well as the third most common cause of cancer mortality. In view of the poor prognosis of unresectable liver cancers, it is of pivotal importance to develop novel chemotherapeutical regimens. RNase MC2 is a 14-kDa ribonuclease isolated from dietary bitter gourd (Momordica charantia) that manifested antitumor potential against breast cancers. In this study, we investigated the potential application of RNase MC2 on Hep G2 cells. We showed that RNase MC2 inhibited cell proliferation and induced cell apoptosis in both in vitro and in vivo studies. RNase MC2 treatment caused cell cycle arrest predominantly at the S-phase and apoptosis, which is associated with the activation of both caspase-8 and caspase-9 regulated caspase pathways. Our further investigation disclosed that RNase MC2 down-regulated the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bak. Moreover, the phosphorylation of ERK and JNK was involved in the apoptosis process. Importantly, RNase MC2 significantly suppressed the growth of Hep G2 xenograft-bearing nude mice by inducing apoptosis. This notion is supported by data indicating an increased number of caspase-3- and PARP-positive cells, and TUNEL-positive cells in RNase MC2-treated tumor tissues. In summary, we have revealed the antitumor potential of RNase MC2 toward Hep G2 cells. Considering that bitter gourd is a common dietary component in many countries, this study may help to prompt the clinical application of RNase MC2.
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PMID:In vitro and in vivo anticarcinogenic effects of RNase MC2, a ribonuclease isolated from dietary bitter gourd, toward human liver cancer cells. 2255 86

The present investigation was undertaken to gain insight into the molecular mechanism by which myricetin induces apoptosis in human hepatocarcinoma HepG2 cells. Myricetin caused the disruption of mitochondrial membrane potential in a dose-dependent manner. Moreover, myricetin triggered translocation of the pro-apoptotic protein Bax to the mitochondria, downregulation of anti-apoptotic Bcl-2 expression and upregulated the expression of pro-apoptotic protein Bad in the mitochondria. The present study also showed that myricetin promoted the release of cytochrome C from mitochondria into the cytosol followed by an increase in the proteolytic activation of caspase-3 and the concomitant degradation of PARP protein. Additionally, western blot analysis showed that the Akt/p70s6k1 pathway was inhibited in myricetin-treated HepG2 cells, accordingly the phosphorylation of Bad at Ser136 was downregulated. Collectively, these findings indicate that myricetin induced apoptosis in HepG2 cell through mitochondria apoptotic pathway and Akt/p70s6k1/Bad signaling. Present results provide new information on the possible mechanisms for the anti-cancer activity of myricetin.
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PMID:Myricetin induces apoptosis in HepG2 cells through Akt/p70S6K/bad signaling and mitochondrial apoptotic pathway. 2343 27

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burden in vivo in a HepG2 tumor xenograft model. Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2. These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy.
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PMID:5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins. 2353 82

Hepatocellular carcinoma (HCC) is a prevalent problem worldwide. Chemotherapy, especially cisplatin (CDDP)-based systemic chemotherapy, is the best option for advanced liver cancer. However, CDDP resistance is becoming common and hindering the clinical application of CDDP. Meanwhile, no consensus has been reached regarding the chemotherapeutic use of vasohibin 2 (VASH2), which promotes the angiogenesis and proliferation of cancer cells. In this work, a tissue microarray was used to observe VASH2 and its possible role in cancer treatment. Results showed that VASH2 was highly expressed in HCC tissues and was significantly correlated with cancer differentiation. To further investigate the efficacy and mechanism of the combination of VASH2 with anti-cancer drugs in liver cancer cells, we stably built VASH2 overexpression and knockdown cell lines. We found that VASH2 can influence the CDDP sensitivity and that the cell overexpression of VASH2 had a higher cell viability and lower apoptosis rate after CDDP exposure. We also observed that VASH2 overexpression downregulated wild-type p53, as well as suppressed the expression of the pro-apoptotic protein BCL2-associated X protein (Bax) and cleaved caspase-3 (CC-3) after treatment by CDDP. Conversely, the knockdown of VASH2 significantly inhibited these effects. In an in vivo chemosensitivity study, nude mice were subcutaneously injected with tumor cells and received CDDP treatment through intraperitoneal administration every 3 days. We found that VASH2 knockdown markedly limited the tumor growth and enhanced the CDDP toxicity and apoptosis of tumor cells. Western blot analysis revealed that tumor cells with downregulated VASH2 had a higher expression of wild-type p53, Bax, and CC-3 than control cells. Overall, our results indicated the novel roles of VASH2 in the chemoresistance of hepatocarcinoma cells to CDDP and suggested that VASH2 may be a promising anticancer target.
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PMID:Vasohibin 2 decreases the cisplatin sensitivity of hepatocarcinoma cell line by downregulating p53. 2459 63


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