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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.
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PMID:Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways. 1903 4

Overexpression of cFLIP protein seems to be critical in the antiapoptotic mechanism of immune escape of human COLO 205 colon adenocarcinoma cells. Actually, cFLIP appears to inhibit the death receptor ligand-mediated cell death. Application of the metabolic inhibitor sodium butyrate (NaBt), short-chain volatile fatty acid, sensitized COLO 205 cells to TNF-alpha-mediated apoptosis. Western-blot analysis revealed that the susceptibility of human COLO 205 cells to apoptogenic stimuli resulted from time-dependent reduction in cFLIP and simultaneous up-regulation of TNF-R1 protein levels. Additionally, the combined TNF-alpha and NaBt treatment caused cleavage of Bid and caspase-9 activation, as well as cytochrome c release from mitochondria. Thus, the evidence of this study indicates that NaBt facilitates the death receptor signal evoked by TNF-alpha. Moreover, NaBt alone initiated intrinsic apoptosis, that in turn was abolished by intracellular BCL-2 delivery. It confirms the involvement of mitochondria in the proapoptotic activity of NaBt. The activation of mitochondrial pathway was substantiated by up-regulated expression of BAK with concomitant reduction of antiapoptotic BCL-x(L), XIAP and survivin proteins. These findings suggest that NaBt could represent a good candidate for the new therapeutic strategy aimed to improve chemo- and immunotherapy of colon cancer.
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PMID:Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-alpha-dependent extrinsic apoptosis. 1913 Feb 37

We observed that treatment of prostate cancer cells for 24 h with magnolol, a phenolic component extracted from the root and stem bark of the oriental herb Magnolia officinalis, induced apoptotic cell death in a dose- and time-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in magnolol-treated cells. Treatment of PC-3 cells with an apoptosis-inducing concentration of magnolol (60 microM) resulted in a rapid decrease in the level of phosphorylated Akt leading to inhibition of its kinase activity. Magnolol treatment (60 microM) also caused a decrease in Ser((136)) phosphorylation of Bad (a proapoptotic protein), which is a downstream target of Akt. Protein interaction assay revealed that Bcl-xL, an anti-apoptotic protein, was associated with Bad during treatment with magnolol. We also observed that during treatment with magnolol, translocation of Bax to the mitochondrial membrane occurred and the translocation was accompanied by cytochrome c release, and cleavage of procaspase-8, -9, -3, and poly(ADP-ribose) polymerase (PARP). Similar results were observed in human colon cancer HCT116Bax(+/-) cell line, but not HCT116Bax(-/-) cell line. Interestingly, at similar concentrations (60 microM), magnolol treatment did not affect the viability of normal human prostate epithelial cell (PrEC) line. We also observed that apoptotic cell death by magnolol was associated with significant inhibition of pEGFR, pPI3K, and pAkt. These results suggest that one of the mechanisms of the apoptotic activity of magnolol involves its effect on epidermal growth factor receptor (EGFR)-mediated signaling transduction pathways.
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PMID:Magnolol induces apoptosis via inhibiting the EGFR/PI3K/Akt signaling pathway in human prostate cancer cells. 1922 60

Fisetin, or 3,3',4',7-tetrahydroxyflavone, is present in fruits and vegetables and has been previously reported to inhibit the proliferation of a variety of cancer cells (Lu X, Jung J, Cho HJ, Lim do Y, Lee HS, Chun HS, Kwon DY, Park JH. J Nutr 135: 2884-2890, 2005). We have demonstrated in a previous work that 20-60 micromol/l fisetin inhibits cyclin-dependent kinase activities resulting in cell cycle arrest in HT-29 colon cancer cells. In the present study, we attempted to characterize the mechanisms by which fisetin induces apoptosis in HCT-116 cells. DNA condensations, cleavage of poly(ADP-ribose) polymerase (PARP), and cleavage of caspases 9, 7, and 3 were induced in HCT-116 cells treated with 5-20 micromol/l of fisetin. Fisetin induced a reduction in the protein levels of antiapoptotic Bcl-xL and Bcl-2 and an increase in the levels of proapoptotic Bak and Bim. Fisetin did not affect the Bax protein levels, but induced the mitochondrial translocation of this protein. Fisetin also enhanced the permeability of the mitochondrial membrane and induced the release of cytochrome c and Smac/Diablo. Additionally, fisetin caused an increase in the protein levels of cleaved caspase-8, Fas ligand, death receptor 5, and TNF-related apoptosis-inducing ligand, and the caspase-8 inhibitor Z-IETD-FMK suppressed fisetin-induced apoptosis and the activation of caspase-3. Furthermore, fisetin increases p53 protein levels, and the inhibition of p53 expression by small interference RNA resulted in a decrease in the fisetin-induced translocation of Bax to the mitochondria, release of mono- and oligonucleosome in the cytoplasm, and PARP cleavage. These results show that fisetin induces apoptosis in HCT-116 cells via the activation of the death receptor- and mitochondrial-dependent pathway and subsequent activation of the caspase cascade. The induction of p53 results in the translocation of Bax to the mitochondria, which contributes to fisetin-induced apoptosis in HCT-116 cells.
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PMID:Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. 1926 55

S-Adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) inhibit mitogen-induced proliferative response in liver and colon cancer cells. SAMe and MTA are also proapoptotic in liver cancer cells by selectively inducing Bcl-x(S) expression. The aims of this work were to assess whether these agents are proapoptotic in colon cancer cells, and if so, to elucidate the molecular mechanisms. We found that both SAMe and MTA are proapoptotic in HT-29 and RKO cells in a dose- and time-dependent manner. Gene microarray uncovered down-regulation of cellular FLICE inhibitory protein (cFLIP). SAMe and MTA treatment led to a decrease in the mRNA and protein levels of both the long and short cFLIP isoforms. This required de novo RNA synthesis and was associated with activation of procaspase-8, Bid cleavage, and release of cytochrome c from the mitochondria. Inhibiting caspase 8 activity or overexpression of cFLIP protected against apoptosis, whereas supplementing with polyamines did not. SAMe and MTA treatment sensitized RKO cells to tumor necrosis factor alpha-related apoptosis-inducing ligand-induced apoptosis. Although SAMe and MTA are proapoptotic in colon cancer cells, they have no toxic effects in NCM460 cells, a normal colon epithelial cell line. In contrast to liver cancer cells, SAMe and MTA had no effect on Bcl-x(S) expression in colon cancer cells. In conclusion, SAMe and MTA are proapoptotic in colon cancer cells but not normal colon epithelial cells. One molecular mechanism identified is the inhibition of cFLIP expression. SAMe and MTA may be attractive agents in the chemoprevention and treatment of colon cancer.
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PMID:S-Adenosylmethionine and methylthioadenosine inhibit cellular FLICE inhibitory protein expression and induce apoptosis in colon cancer cells. 1937 10

A secondary bile acid, namely, deoxycholic acid (DCA), has been known to promote colon tumors; on the other hand, it also induces apoptosis in several human colon cancer cell lines. A hydrophobic primary bile acid, namely, chenodeoxycholic acid (CDCA), exhibits a similar property of apoptosis induction; DCA and CDCA also trigger some specific intracellular signal pathways in the human colon cancer cell line HCT116. In this article, we report that hydrophobic bile acids induce different cellular responses depending on their concentration, that is, a sublethal concentration of hydrophobic bile acids can suppress the apoptosis induced by a higher concentration of DCA. Pretreatment with DCA or CDCA at a concentration of < or = 200 microM for 8 h suppressed the apoptosis induced by 500 microM DCA in HCT116 cells. Under this condition, the association of caspase-9 and Apaf-1 and subsequent activation of caspase-9 were inhibited, but the release of cytochrome c from the mitochondria was not. At 200 microM, DCA and CDCA induced the phosphorylation of Akt and ERK1/2, although these phosphorylations do not appear to be indispensable for the cytoprotection. It is interpreted that prolonged exposure to sublethal concentrations of hydrophobic bile acids induces resistance to apoptosis, leading to promotion of colorectal tumorigenesis.
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PMID:Biphasic regulation of cell death and survival by hydrophobic bile acids in HCT116 cells. 1937 11

Butyrate is an inhibitor of histone deacetylase (HDAC) and has been extensively evaluated as a chemoprevention agent for colon cancer. We recently showed that mutations in the adenomatous polyposis coli (APC) gene confer resistance to HDAC inhibitor-induced apoptosis in colon cancers. Here, we show that APC mutation rendered colon cancer cells resistant to butyrate-induced apoptosis due to the failure of butyrate to down-regulate survivin in these cells. Another cancer-preventive agent, 3,3'-diindolylmethane (DIM), was identified to be able to down-regulate survivin in colon cancers expressing mutant APC. DIM inhibited survivin mRNA expression and promoted survivin protein degradation through inhibition of p34(cdc2)-cyclin B1-mediated survivin Thr(34) phosphorylation. Pretreatment with DIM enhanced butyrate-induced apoptosis in colon cancer cells expressing mutant APC. DIM/butyrate combination treatment induced the expression of proapoptotic Bax and Bak proteins, triggered Bax dimerization/activation, and caused release of cytochrome c and Smac proteins from mitochondria. Whereas overexpression of survivin blocked DIM/butyrate-induced apoptosis, knocking down of survivin by small interfering RNA increased butyrate-induced apoptosis in colon cancer cells. We further showed that DIM was able to down-regulate survivin and enhance the effects of butyrate in apoptosis induction and prevention of familial adenomatous polyposis in APC(min/+) mice. Thus, the combination of DIM and butyrate is potentially an effective strategy for the prevention of colon cancer.
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PMID:3,3'-diindolylmethane enhances the efficacy of butyrate in colon cancer prevention through down-regulation of survivin. 1947 Jul 89

Cancer is one of the leading causes of death in the world. The triterpenoid compound asiatic acid derived from the tropical medicinal plant Centella asiatica displays cytotoxic activity on fibroblast cells and several other kinds of cells. The present work studies asiatic acid-mediated growth inhibition of cancer cells and the underlying mechanism. Asiatic acid markedly inhibited cancer cell proliferation. Apoptosis of SW480 human colon cancer cells was induced by asiatic acid as shown by flow cytometry, DNA fragmentation and nuclear chromatin condensation experiments. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria into cytosol, asiatic acid induced caspase-9 activity, which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage resulting in irreversible apoptotic death in the tumor cells. Taken together, these results suggest that mitochondrial death apoptosis cascade plays very important roles in asiatic acid-induced cancer apoptosis.
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PMID:Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade. 1965 80

Earlier we showed that RACK1 regulates growth of human colon cells by suppressing Src activity at G(1) and mitotic checkpoints. Here, we show that RACK1 also induces apoptosis of the cells, partly by inhibiting Src. In the intrinsic pathway, RACK1 inhibits expression of anti-apoptotic Bcl-2 and Bcl-X(L), induces expression of pro-apoptotic Bim, targets Bim and Bax to the mitochondria, induces oligomerization of Bax (which requires Bim and inhibition of Src), depolarizes mitochondria membranes, releases cytochrome c, and activates caspases-9 and -3 and death substrates. Bax and Bim are required for RACK1-mediated mitochondrial cell death. RACK1-induced oligomerization of Bax is required for staurosporine-mediated cell death. RACK1 also induces apoptosis by blocking Src activation of the Akt cell survival pathway. This leads to activation of the transcription factor FOXO3, a potent inducer of apoptosis and G(1) arrest. Collectively, our results show that RACK1, partly by inhibiting Src, promotes mitochondrial cell death and blocks Akt-mediated cell survival. Thus, RACK1 inhibits growth and induces death of colon cells. Exploitation of these dual functions could lead to novel colon cancer therapies that mimic RACK1 function.
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PMID:A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways. 2069 60

We analyzed the apoptosis and anti-tumour activities of several Mn(III)-salen and -salphen complexes (1-14) towards three different cultured human cancer and non-cancer cells. We demonstrated that most of the Mn(III)-salen and -salphen complexes affect cell viability and induce apoptosis in MCF7 cells. Biochemically active Mn(III)-salen and -salphen complexes induced nuclear fragmentation and release of cytochrome c from the mitochondria to cytosol indicating involvement of mitochondrial pathway of apoptosis. The nature and position of the substituents and the bridging group on the salen ligands play crucial roles in determining the apoptotic activities of Mn(III)-salen and -salphen complexes. The IC50 values for the active Mn(III)-salen complexes ranged between 12 and 55 microM. For Mn(III)-salen complexes with ethylenediamine bridges, methoxy substituted complexes were more active than the corresponding hydroxy derivatives. However, this correlation does not hold when the bridging group was changed from ethylenediamine to o-phenylenediamine. Importantly, several Mn(III)-salen and -salphen complexes showed about 2-3 fold selectivity toward cancer cells such as MCF7 (breast cancer), and CCL228 (colon cancer) over a normal non-malignant cell MCF10 (breast epithelial cells) indicating their potential application towards novel anti-tumour therapy.
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PMID:Apoptosis and anti-tumour activities of manganese(III)-salen and -salphen complexes. 1980 27


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