Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the roles of ERK1/2 mitogen-activated protein kinase in vitamin E succinate (VES)-induced apoptosis in human gastric cancer SGC-7901 cells, apoptosis was observed by DAPI staining and the phosphorylation of ERK1/2 by VES at different doses and different time points was measured by western blot. The results showed that VES obviously induced cells to undergo apoptosis and apoptotic rate after 24 h and 48 h of treatment with VES at 20 micrograms/ml. VES was 14.2% and 89.4%, respectively. The expression of p-ERK was evidently reduced by VES at 5, 10 and 20 micrograms/ml for 24 h. ERK1/2 was immediately activated by VES at 20 micrograms/ml, but the expression was decreased for 2 h, then increased again and reached the top level for 12 h. The data implicated that ERK1/2 pathway might be involved in VES-induced apoptosis, but in the proliferation eventually.
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PMID:[Roles of ERK1/2 MAPK in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells]. 1496 7

APOBEC3G and 3F (A3G and A3F) cytidine deaminases incorporate into retroviral cores where they lethally hypermutate nascent DNA reverse transcripts. As substantiated here, the viral infectivity factor (Vif) encoded by human immunodeficiency virus type-1 (HIV-1) binds A3G and A3F and induces their degradation, thereby precluding their incorporation into viral progeny. Previous evidence suggested that A3G is expressed in H9 and other nonpermissive cells that contain this antiviral defense but not in several permissive cells, and that overexpression of A3G or A3F makes permissive cells nonpermissive. Using a broader panel of cell lines, we confirmed a correlation between A3G and cellular abilities to inactivate HIV-1(Deltavif). However, there was a quantitative discrepancy because several cells with weak antiviral activities had similar amounts of wild-type A3G mRNA and protein compared to H9 cells. Antiviral activity of H9 cells was also attenuated in some conditions. These quantitative discrepancies could not be explained by the presence of A3F or other A3G paralogs in some of the cell lines. Thus, A3A, A3B, and A3C had weak but significant anti-HIV-1 activities and did not dominantly interfere with A3G or A3F antiviral functions. Control of A3G synthesis by the protein kinase C/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway was also similar in permissive and nonpermissive cells. A3G in highly permissive cells is degraded by Vif, suggesting that it is not in a sequestered site, and is specifically incorporated in low amounts into HIV-1(Deltavif). Although A3G and/or A3F inactivate HIV-1(Deltavif) and are neutralized by Vif, the antiviral properties of cell lines are also influenced by other cellular and viral factors.
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PMID:Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. 1606 Aug 32

Gastric neoplastic disease is one of the most frequent causes of cancer-associated deaths with poor prognosis. Here we studied the effect of the redox-silent analogue alpha-tocopheryl succinate (alpha-TOS), a strong apoptogen and anti-cancer agent, on the gastric cancer cell line SGC-7901. alpha-TOS inhibited proliferation of the cells and induced their apoptosis in a concentration- and time-dependent manner, while succinate or alpha-tocopherol showed no effect. The effect of alpha-TOS was modulated by components of the MAPK signaling network, including ERK1/2 and c-Jun N-terminal kinase (JNK), but not p38. Activation of ERK1/2 occurred early and increased until 12h, coinciding with an in crease in apoptosis in the cells, after which it dropped abruptly, while activation of JNK rose steadily, reaching a plateau at 12h of alpha-TOS treatment. The effects of ERK1/2 and JNK on the apoptosis outcome are transmitted via c-Jun, since transfection of the cells with c-Jun antisense oligodeoxynucleotide inhibited alpha-TOS-induced apoptosis. We conclude that ERK1/2 and JNK positively regulate apoptosis induced in gastric cancer cells by alpha-TOS.
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PMID:alpha-Tocopheryl succinate-induced apoptosis in human gastric cancer cells is modulated by ERK1/2 and c-Jun N-terminal kinase in a biphasic manner. 1683 62

Tocotrienols have been shown to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in tocotrienol-induced apoptosis are still unclear. In the present study, gamma-tocotrienol induced apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down regulation of the extracellular signal-regulated kinase (ERK) signalling pathway. Furthermore, gamma-tocotrienol-induced apoptosis was accompanied by down regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up or down regulation of Bcl-2 family proteins play a major role in the initiation of gamma-tocotrienol-induced apoptosis as an activator of caspase-3. Gamma-tocotrienol also down regulated the activation of the Raf-ERK signalling pathway, and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2 proteins. The results suggest that key regulators in tocotrienol-induced apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down regulation of the Raf-ERK signalling pathway.
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PMID:Gamma-tocotrienol-induced apoptosis in human gastric cancer SGC-7901 cells is associated with a suppression in mitogen-activated protein kinase signalling. 1808 43

Vitamin E succinate (RRR-alpha-tocopheryl succinate, VES), an efficient inducer of apoptosis, acts as a potent agent for cancer therapy. However, the mechanism by which VES mediates the effects are not yet fully understood. Here we studied the effect of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) on VES-induced apoptosis of SGC-7901 human gastric cancer cells. VES caused cytological changes typical of apoptosis, increased ER dilation and cytosolic Ca(2+) concentration. And endogenous ER stress markers, GRP78 and GRP94 were transcriptionally and translationally altered. In response to VES, induction of CHOP, activation of caspase-4 and JNK were observed. Furthermore, VES also triggered activation of UPR components, including RNA-dependent protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), X-box-binding protein 1 (XBP1), and ATF4 in a concentration- and time-dependent manner. Consequently, our results suggest that VES-induced apoptosis is coupled to ER stress and UPR activation in SGC-7901 human gastric cancer cells.
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PMID:Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells. 2043 8

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.
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PMID:gamma-Tocotrienol modulates the paracrine secretion of VEGF induced by cobalt(II) chloride via ERK signaling pathway in gastric adenocarcinoma SGC-7901 cell line. 2045 89

PURPOSE : Treatment effects of advanced gastric cancer (AGC) are unsatisfactory, and novel therapeutic approaches are much needed. The epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab inhibits the growth of several human cancer cells but has been tested rarely for the treatment of GC. The synergy between cetuximab and irinotecan has been reported in colorectal cancer, but the mechanisms are still not fully clarified. Consequently, we hypothesized cetuximab/irinotecan combination should enhance the antitumor activity of irinotecan in GC cells. METHODS : The in vitro antiproliferative, pro-apoptotic, cell cycle arrest effects and induction of senescence were examined in SGC-7901 and MKN-45 GC cell lines. The effects of cetuximab or irinotecan as single agents or the combination on the expression of p53, p16, and EGFR signaling pathways were also studied. RESULTS : The study revealed that cetuximab alone did not show any antiproliferative, pro-apoptotic, cell cycle arrest or cellular senescence effect on GC cells but when combined with irinotecan synergistically inhibits GC cell proliferation and induces apoptosis and G2/M phase arrest. Irinotecan increases phosphorylation of EGFR, MAPK, and AKT and decreases the expression of P27(Kip1), which could be all abrogated by its combination with cetuximab. The combination could also inhibit the expression of Cyclin D1 and phosphorylated mTOR while had no impact on p53, p16, PTEN, and HIF-1alpha. CONCLUSIONS : Cetuximab enhances the activities of irinotecan on GC cells via the downregulation of the EGFR pathway upregulated by irinotecan. Combination therapy with cetuximab and irinotecan, a novel therapeutic approach, warrants further study in GC.
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PMID:Cetuximab enhances the activities of irinotecan on gastric cancer cell lines through downregulating the EGFR pathway upregulated by irinotecan. 2128 18

To investigate the inhibition effect of Ganoderma applanatum extract (GAEAE) on human gastric cancer cell lines and apoptosis mechanism, Alamar Blue assay was used to assess the inhibition and apoptosis-inducing effect of the GAEAE on proliferation of SGC-7901 cells, the DNA ladders of the apoptosis cells was done, the mRNA expression of p53, Bax, Bcl-2 and JNK were analysed by reverse transcription-polymerase chain reaction. The levels of the Cyt C and the p53, Bax/Bcl-2, JNK proteins and the caspase-3 activity in the SGC-7901 cells were measured with ELISA kits. Our data showed that the GAEAE markedly inhibited the proliferation of SGC-7901 cells in a dose-dependent manner. The expression of Bcl-2 protein was down-regulated and Bax, c-jun, p53 protein expressions were up-regulated by the GAEAE treatment in SGC-7901 cells. The activity of caspase-3 was markedly increased and the Cty C was markedly released into cytoplasm from the mitochondria after GAEAE action. In conclusion, our results indicated that the GAEAE could enhance the sensitivity of SGC-7901 cells to the c-jun, p53, Bax and Bcl-2 induced apoptosis and provided a promising approach to anti-human gastric cancer therapy with Ganoderma applanatum.
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PMID:Cellular and molecular mechanisms of the Ganoderma applanatum extracts induces apoptosis on SGC-7901 gastric cancer cells. 2146 94

The aim of the present study was to observe the influence of various factors on the nuclear distribution of the RhoA protein in the SGC-7901 human gastric cancer cell line. Immunofluorescence microscopy was used to detect the localization of the RhoA protein, and Western blotting was used to determine the quantity of RhoA in the nucleus, cytosol and membrane. The results showed that H2O2-mediated damage and a lipopolysaccharide (LPS)-mediated inflammatory reaction caused the translocation of RhoA from the cytosol toward the nucleus. A P38 mitogen-activated protein kinase (MAPK) inhibitor effectively hindered the LPS-triggered translocation of RhoA into the nucleus at the initial stage. Furthermore, the microtubule-targeted anticancer drug Taxol triggered the translocation of RhoA from the nucleus toward the cytosol and membrane, and Lysophosphatidic acid (LPA) enhanced this translocation. A protein modification inhibitor and a nucleus export inhibitor had no obvious effect on RhoA distribution in the nucleus. The results revealed that the distribution of RhoA protein in the nucleus was influenced by factors related to cell activities but was not affected by the modification of the protein. The translocation of RhoA into the nucleus was not dependent on the active nuclear import system.
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PMID:Factors influencing RhoA protein distribution in the nucleus. 2185 Mar 73

In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on "reprogramming" of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression.
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PMID:Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth. 2190 Jul 53


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