Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the crude extract of Solanum lyratum (SLE) on human colon cancer colo 205 cells were investigated. The cell viability, morphological changes of the cells, cell cycle arrest, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (deltapsi(m)) and cell cycle- and apoptosis-associated protein levels and gene expressions were examined in colo 205 cells after exposure to various concentrations of SLE for different time periods. The results indicated that SLE decreased the percentage of viable colo 205 cells accompanied by morphological changes. The most effective concentration of SLE was 300 pg/ml (SLE 300) and this concentration was used for further investigations. SLE induced S-phase arrest and apoptosis (sub-G1) in the colo 205 cells and those effects were dose- and time-dependent. DAPI staining and DNA gel electrophoresis confirmed that SLE induced apoptosis in colo 205 cells. Flow cytometric analysis also showed that SLE 300 promoted ROS production and decreased the deltapsi(m). Western blotting analysis indicated that SLE 300 increased Bax levels and decreased Bcl-2 levels, which caused the loss of deltapsi(m) followed by cytochrome c release and caspase-9 and -3 activation, finally leading to apoptosis. SLE 300 also promoted p53 and p27, but decreased the levels of cyclin B1 thus causing S-phase arrest. The gene expression associated with those proteins was also confirmed by PCR methods. The findings show that SLE might be used as a colon cancer therapeutic agent in the future.
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PMID:Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205). 1850 53

This study examined the apoptotic effects of crude saponins acquired from the roots of Platycodon grandiflorum (SPR) in HT-29 human colon cancer cells. SPR decreased HT-29 cell proliferation in dose- and time-dependent manners by inducing apoptosis via DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. The apoptosis induced by SPR was associated with the activation of initiator caspases-8 and -9, as well as the effector caspase-3. SPR stimulated Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. SPR increased the expression of the pro-apoptotic protein, Bax, and decreased the expression of the anti-apoptotic protein, Bcl-2. SPR also increased the expression of the caspase-independent mitochondrial apoptosis factor, AIF, in HT-29 cells. These results indicate that SPR inhibits HT-29 cell proliferation by inducing apoptosis, which may be mediated via both caspase-dependent and -independent pathways.
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PMID:Induction of apoptosis in HT-29 colon cancer cells by crude saponin from Platycodi Radix. 1895 3

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

The polycation poly(ethylenimine) (PEI) was used to deliver the plasmids coding for various combinations of caspases to Cox-2 overexpressing cancer cell lines. It was found that the expression of the delivered genes, controlled by the Cox-2 promoter, correlated with the expression of the endogenous Cox-2 gene in each cell line in a relatively linear manner. Among the various caspase combination regimens, the combination of caspase 3 plus caspase 9 proved to be the most effective because of an apparent synergy between the two gene products, and produced phosphatidylserine flipping in addition to fragmentation of genomic DNA. Caspase 1 appeared to work independently of either caspases 3 or 9, as no synergistic effect was observed. Transfections with genes coding for granzyme B and caspase 8 yielded a lesser amount of cell death. The delivery of a combination of caspase genes could be readily moved to in vivo research of bladder and colon cancer treatments, and holds great applicability to a wide array of additional tumor types.
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PMID:Comparison of caspase genes for the induction of apoptosis following gene delivery. 1906 54

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

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

Glycoconjugates represent a recent trend in cancer chemotherapy that adopts the concept of selective prodrug/drug targeting of tumor cells by selectively binding to specific transmembrane glucose transporters. Following preferential uptake of sugar conjugates into cancer cells, they are presumably subject to enzymatic cleavage by specific beta-glycosidases to liberate the free active cytotoxic aglycones that act selectively on cancer cells and spare other noncancerous ones. In this sense, the cytotoxicity of an array of newly synthesized glycoconjugates, including curcumin beta-glucoside, perillyl alcohol beta-glucoside, perillyl alcohol beta-galactoside, diethylstilbesterol beta-glucoside and diethylstilbesterol beta-galactoside have been investigated over 24-96 h in a panel of human colon cancer cells namely, Caco-2, HT29 and T84 cells. The role of beta-glycosidases and caspases in the bioactivation and cytotoxicity of these compounds has been addressed in the current study. All the glycoconjugates have proven cytotoxic efficacy in a time-dependent manner. Curcumin beta-glucoside was the most potent amongst all glycoconjugates tested. The sensitivity rank order of tumor cells towards all beta-glucosides was Caco-2 > HT29 > T84. This sensitivity ranking was well correlated with beta-glucosidase activity assessed in these cell lines. Unlike perillyl alcohol galactoside, the cytotoxicity rank order for diethylstilbesterol beta-galactoside was not coping with the beta-galactosidase activity detected. Apoptosis was assessed by fluorometric assay of caspase-3 and caspase-9 activities. Initiation and activation of apoptosis were increased in all colon cancer cells following exposure to most of the glycoconjugates, and this was well correlated with the cytotoxicity rank order of these prodrugs. Enzymatic cleavage of glycoconjugates was accomplished using a host of hydrolytic enzymes and cleavage kinetics was determined using HPLC. The glycoconjugates were only cleaved by beta-glucosidases and beta-galactosidases, but not by pancreatic lipase or hepatic esterase. Taken together, one could conclude that beta-glucosidases and beta-galactosidases are crucial for the bioactivation and cytotoxicity of these glycoconjugates. Also, initiation and activation of apoptosis in tumor cells may contribute, at least partly, for the cytotoxicity of these sugar conjugates.
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PMID:Possible contribution of beta-glycosidases and caspases in the cytotoxicity of novel glycoconjugates in colon cancer cells. 1941 82

This study was performed to elucidate the apoptotic pathways by thiosulfinates, major biologically active components of Allium tuberosum L., in HT-29 human colon cancer cells. Thiosulfinates significantly induced cell death in dose- and time-dependent manners in HT-29 cells, which is associated with apoptosis. Thiosulfinates activated the initiator caspase-8, and -9, and the effector caspase-3. In the present study, thiosulfinates were found to stimulate Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thiosulfinates down-regulated the expression of the anti-apoptotic protein Bcl-2, and up-regulated the expression of the pro-apoptotic protein Bax. We also found that thiosulfinates increased the expression of AIF, a caspase-independent mitochondrial apoptosis factor, and induced DNA fragmentation and chromatin condensation in HT-29 cells. These results indicate that thiosulfinates from A. tuberosum L. inhibited cell proliferation and activated both the caspase-dependent and caspase-independent apoptotic pathways in HT-29 cells.
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PMID:Mechanisms of thiosulfinates from Allium tuberosum L.-induced apoptosis in HT-29 human colon cancer cells. 1944 47

Ginsenoside Rg3, the main constituent isolated from Panax ginseng, has been of interest for use as a cancer preventive or therapeutic agent. We investigated here whether Rg3 can inhibit the activity of NF-kappaB, a key transcriptional factor constitutively activated in colon cancer that confers cancer cell resistance to chemotherapeutic agents. To investigate whether RG3 can suppress activation of NF-kappaB, and thus inhibit cancer cell growth, we examined the susceptibility of colon cancer cells (SW620 and HCT116) to treatment with Rg3 (25, 50, 75, 100 microM) and RG3-induced activation of NF-kappaB. RG3 dose-dependently inhibited cancer cell growth through induction of apoptosis and decreased NF-kappaB activity. In a further study of compounds in colon cancer, we used half of the IC(50) dose, values in combined treatments of Rg3 (50 microM) with conventional agents - docetaxel (5 nM), paclitaxel (10 nM) cisplatin (10 microM) and doxorubicin (2 microM). Compared to treatment with Rg3 or chemotherapy alone, combined treatment was more effective (i.e., there were synergistic effects) in the inhibition of cancer cell growth and induction of apoptosis and these effects were accompanied by significant inhibition of NF-kappaB activity. NF-kappaB target gene expression of apoptotic cell death proteins (Bax, caspase-3, caspase-9) was significantly enhanced, but the expression of anti-apoptotic genes and cell proliferation marker genes (Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), Cox-2, c-Fos, c-Jun and cyclin D1) was significantly inhibited by the combined treatment compared to Rg3 or docetaxel alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and enhances the susceptibility of colon cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer or adjuvant anti-cancer agent.
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PMID:Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. 1947 91

We examined the interaction between the multikinase inhibitor sorafenib and histone deacetylase inhibitors. Sorafenib and vorinostat synergized (sorafenib + vorinostat) to kill HCT116 and SW480 cells. In SW480 cells, sorafenib + vorinostat increased CD95 plasma membrane levels and promoted death-inducing signal complex (DISC) formation, and drug toxicity was blocked by knockdown of CD95 or overexpression of cellular FLICE-like inhibitory protein (c-FLIP-s). In SW620 cells that are patient-matched to SW480 cells, sorafenib + vorinostat toxicity was significantly lower, which correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and enhanced tumor cell killing, whereas knockdown of LASS6 in SW480 cells suppressed CD95 activation. Knocking down LASS6 expression also suppressed CD95 activation in hepatoma, pancreatic, and ovarian cancer cells. In HCT116 cells, sorafenib + vorinostat treatment caused DISC formation without reducing c-FLIP-s expression and did not increase CD95 plasma membrane levels; sorafenib + vorinostat exposure killed HCT116 cells via an intrinsic pathway/caspase 9-dependent mechanism. In HCT116 cells, knockdown of CD95 enhanced sorafenib + vorinostat lethality, which correlated with less drug-induced CD95-dependent autophagy. Sorafenib + vorinostat treatment activated the c-Jun NH(2)-terminal kinase pathway, which was causal in promoting dissociation of Beclin1 from BCL-2, and in promoting autophagy. Knockdown of Beclin1 expression blocked autophagy and enhanced drug toxicity. Our data demonstrate that treatment of colon cancer cells with sorafenib + vorinostat activates CD95 via de novo ceramide synthesis that promotes viability via autophagy or degrades survival via either the extrinsic or intrinsic pathways.
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PMID:Sorafenib and vorinostat kill colon cancer cells by CD95-dependent and -independent mechanisms. 1948 4


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