Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.
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PMID:Apoptin-induced apoptosis: a review. 1463 34

p16(INK4a) (hereafter referred to as p16), a major cyclin-dependent kinase (CDK) inhibitor, is the product of a tumor-suppressor gene that has been found inactivated in different cancer types. In the present study, we sought to investigate the role of p16 in apoptosis induced by ultraviolet light (the most important etiological cause of skin cancer) and cisplatin (an anticancer DNA damaging agent). It is clearly shown that p16-compromised osteosarcoma U2OS cell line and p16-/- mouse embryo fibroblasts are sensitive to UV-induced apoptosis, as compared to their respective isogenic p16-expressing cells (EH1, EH2) and p16 +/+, indicating that p16 protects cells from undergoing apoptosis in response to UV light. Importantly, this reduction in UV-mediated apoptosis was associated with downregulation of the proapoptotic Bax protein, with no effect on Bcl-2 expression, suggesting that this antiapoptotic role of p16 is mediated via the intrinsic-mitochondrial pathway. On the other hand, p16 sensitized cells to cisplatin-mediated apoptosis through Bcl-2 decline. Interestingly, only proliferating but not G1-arrested EH1 cells underwent apoptosis in response to the anticancer drug. These novel findings provide further insight into the role of p16 in carcinogenesis, and has potential implications for future therapy strategies.
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PMID:The tumor suppressor p16(INK4a) gene is a regulator of apoptosis induced by ultraviolet light and cisplatin. 1471 25

Glucocorticoids have marked effects on bone metabolism, and continued exposure of skeletal tissue to excessive amounts of these steroids results in osteoporosis. Therefore, in the present proteomic study, we characterized the potential effects of glucocorticoids on protein expression in human osteoblastic cells. Using two-dimensional gel electrophoresis and mass spectrometry, we identified an increased expression of glutamine synthetase (GS) in dexamethasone (Dex)-treated human MG-63 osteosarcoma cells. GS is an enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Intracellular and extracellular glutamate levels may be important in cell signalling mediated by glutamate transporters and receptors which have recently been found in bone cells. The induction of GS protein by Dex was accompanied by an increase in mRNA level and enzyme activity. Dex induction of GS was also mediated by glucocorticoid receptors (GRs) because it was blocked by the GR antagonist RU-38486. In addition, Dex induction of GS expression was partially blocked by cyclohexamide indicating that it at least partly required new protein synthesis. GS induction by Dex was not associated with apoptosis as determined by Bax/Bcl-2 ratio and DNA staining. In addition to MG-63 cells, Dex induction of GS was also observed in human G-292 osteosarcoma cells as well as conditionally immortalized human preosteoblastic (HOB-03-C5) and mature osteoblastic (HOB-03-CE6) cells. However, in two other human osteosarcoma cell lines, SaOS-2 and U2-OS, GS expression was not affected by Dex. This observation may be explained by the lower levels of GR protein in these cells. In summary, this is the first report of the regulation of GS expression by glucocorticoids in bone cells. The role of GS in bone cell metabolism and glucocorticoid action on the skeleton is not yet known, but as a modulator of intracellular glutamate and glutamine levels, it may have an important role in these processes.
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PMID:Glucocorticoids induce glutamine synthetase expression in human osteoblastic cells: a novel observation in bone. 1496 10

Functional expression cloning is a powerful strategy for identifying critical steps in biological pathways independently of prior assumptions. It is particularly suitable for the identification of molecules crucial to the control of apoptosis. Our screen for sequences suppressing T-cell apoptosis isolated a sequence antisense to fau (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene). The fox gene in FBR murine osteosarcoma virus is also antisense to fau and several reports have indicated that fau displays tumour suppressor and oncogenic properties in different contexts. Our observations indicate that the fau antisense sequence suppresses expression of endogenous fau mRNA and produces resistance to apoptosis induced both by the glucocorticoid analogue dexamethasone' by ultraviolet radiation, and by the anticancer drug cisplatin. In all cases, colony-forming ability is protected, indicating that fau affects the critical events prior to commitment to cell death. Overexpression of fau in the sense orientation induces cell death, which is inhibited both by Bcl-2 and by inhibition of caspases, in line with its proposed role in apoptosis.
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PMID:Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression. 1554 34

Fluorine compounds are widely used for the prevention of caries, and recently sodium fluorosilicate has been used in water fluorination. The cytotoxic effects of sodium fluorosilicate in several osteosarcoma and oral cancer cells were evaluated in this study by measurement of inhibition of cell proliferation. Human osteogenic sarcoma (HOS) cells were the most sensitive to sodium fluorosilicate treatment. Induction of apoptosis, such as nucleosomal DNA fragmentation and the appearance of apoptotic bodies, were observed in HOS cells by agarose gel electrophoresis and by flow cytometric analysis, respectively. The molecular mechanism of apoptosis induction in HOS was investigated by Western blot analysis. The level of Bcl-2 was decreased and consequent release of cytochrome c was increased. Caspase-3 was activated and the cleavage of poly (ADP-ribosyl) polymerase was increased. In conclusion, sodium fluorosilicate induces apoptosis in HOS cells through decrease in Bcl-2, the release of cytochrome c to the cytosol and activation of caspase-3.
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PMID:Induction of apoptosis by sodium fluorosilicate treatment in human osteogenic sarcoma (HOS) cells. 1581 63

The purpose of this study was to evaluate the anti-tumor effects of osteosarcoma (HOSM-1) cells via transfer of the Bax gene using a cationic liposome. We evaluated the levels of Bax, Bcl-xL, Bcl-2 and cytochrome c expression by Western blot analysis, and caspase-9 and -3 activities were determined in a colorimetric assay. Apoptosis was detected using a TUNEL assay, and cell growth inhibition was determined in an MTT assay. Following Bax gene transfer, release of cytochrome c to the cytosol was detected, the activities of caspase-9 and -3 increased, and TUNEL-positive cells (37.5%) were detected. Cell survival rate was 50.8% under these conditions. Induction of apoptosis was inhibited by a caspase inhibitor (zVAD-fmk), but only a slight increase in cell survival rate occurred. Hence, since not only apoptosis but also caspase-independent cell death is induced in HOSM-1 cells, we anticipate that Bax gene therapy with cationic liposomes will be useful for osteosarcoma.
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PMID:Antitumor activity of cationic liposome-mediated Bax gene transfer in osteosarcoma cells: induction of apoptosis and caspase-independent cell death. 1601 Apr 25

As a low molecular weight redox protein elaborated from the pathogenic bacteria Pseudomonas aeruginosa, azurin is one of representative bacterial products applied in the treatment of tumour. We found that the growth of U2OS cells was significantly inhibited by azurin in a dose-dependent manner with the IC(50) value of 114.54+/-7.65 mgl(-1). But the growth of MG63 cells or L02 cells was almost not inhibited by azurin (P<0.05). Moreover, when treated with azurin, U2OS cells showed typical apoptotic morphological features observed by fluorescent microscopy (AO and Hoechst 33258) and transmission electron microscopy. Typical DNA "ladder" bands were also observed. The apoptosis rate was 35.8% tested by fluorescence-activated cell sorter (Annexin-V-FITC(+)/PI(-)) and the cell-cycle arrested in G(1) phase. But no apoptotic features were observed in control cells. The down-regulation of Bcl-2 (an inhibitor of apoptosis) were detected in U2OS cells when azurin was added for 24h. In contrast, the level of Bax and caspase-3 were significantly up-regulated. So we concluded that azurin could selectively induce apoptosis of human osteosarcoma U2OS cells and the induction of apoptosis by azurin was closely associated with down-regulation of Bcl-2, up-regulation of Bax and activation of caspase-3.
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PMID:Bacterial redox protein azurin induce apoptosis in human osteosarcoma U2OS cells. 1602 99

To elucidate the possible effect of NFkappaB on radioresistance, we used the osteosarcoma cell line Saos2, stably expressing the NFkappaB constitutive inhibitor, mIkappaB (Saos2-mIkappaB) or stably transfected with the empty vector (Saos2-EV). Ionizing radiation induced "intrinsic" apoptosis in Saos2-mIkappaB cells but not in Saos2-EV control cells, with intact NFkappaB activity. We find as expected, that this NFkappaB activity was enhanced following irradiation in the Saos2-EV control cells. On the other hand, inhibition of NFkappaB signaling in Saos2-mIkappaB cells led to the upregulation of the pro-apoptotic systems, such as Bax protein and c-Jun N-terminal Kinase (JNK)/c-Jun/AP1 signaling. Inhibition of NFkappaB resulted in decreased expression of the DNA damage protein GADD45beta, a known inhibitor of JNK. Subsequently, JNK activation of c-Jun/AP-1 proteins increased radiation-induced apoptosis in these mutants. Radiation-induced apoptosis in Saos2-mIkappaB cells was inhibited by the JNK specific inhibitor SP600125 as well as by Bcl-2 over-expression. Furthermore, release of cytochrome-c from mitochondria was increased and caspase-9 and -3 were activated following irradiation in Saos2-mIkappaB cells. Antisense inhibition of GADD45beta in Saos2-EV cells significantly enhanced apoptosis following irradiation. Our results demonstrate that radioresistance of Saos2 osteosarcoma cells is due to NFkappaB-mediated inhibition of JNK. Our study brings new insight into the mechanisms underlying radiation-induced apoptosis of osteosarcoma, and may lead to development of new therapeutic strategies against osteosarcoma.
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PMID:Increased radiation-induced apoptosis of Saos2 cells via inhibition of NFkappaB: a role for c-Jun N-terminal kinase. 1616 36

A major concern in clinical treatment of cancers is resistance of tumors such as hepatocellular carcinoma (HCC) and osteosarcoma to current chemotherapy protocols. Here, we reported that overexpression of second mitochondria-derived activator of caspase (Smac) sensitized osteosarcoma cells and HCC cells in vitro to chemotherapeutic drugs-induced apoptosis. Constitutive expression of Smac resulted in enhanced Bax accumulation on mitochondria upon etoposide stimulation and inhibited Bcl-2-induced antiapoptosis activity. Thus, Smac would sensitize tumor cells to chemotherapeutic drugs in part through promoting Bax translocation to mitochondria and bypassing Bcl-2 block. Moreover, we demonstrated that blockade of Smac expression by antisense smac did not impair etoposide-induced apoptosis; however, p53-induced apoptosis was impaired in smac deficient Saos-2 cell. This suggested Smac might be required in p53-induced apoptosis. Most importantly, complete eradication of HepG2 xenografts in vivo was achieved upon combined therapy with Ad-Smac and 5-Fu. Thus, overexpression of Smac in tumor cells might be a potent strategy for cancer treatment by sensitization of tumor cells to chemotherapeutic drugs.
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PMID:Transfection of Smac sensitizes tumor cells to etoposide-induced apoptosis and eradicates established human hepatoma in vivo. 1621 Oct 87

Many studies have suggested that dietary flavonoids are anticancer agents that induce the apoptosis of cancer cells. However, the effects of flavonoids on the induction of apoptosis in osteosarcoma cells are unclear. Previously, a flavonoid fraction, consisting mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein, herein named RCMF (the RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS). This study evaluated the effects of RCMF on the proliferation and apoptosis using human osteosarcoma (HOS) cells. The mechanism of growth inhibition of the HOS cells by the flavonoid fraction, RCMF, was also assessed. The results demonstrated that RCMF exhibited sensitive growth inhibition and induced apoptosis in HOS cells. PARP cleavage was closely associated with the RCMF-induced apoptosis of the HOS cells. Furthermore, the activation of caspase 8 and Bax, the inhibition of Bcl-2 expression, and the release of cytochrome c are believed to be involved in the RCMF-mediated apoptosis. Collectively, these findings suggest that RCMF is an agent which may be capable of inducing sensitive growth inhibition and apoptosis in HOS cells.
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PMID:Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. 1621 62


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