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)

Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha-aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6, desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2 (P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of the analogs was butanoylated at the N-terminus. The antiproliferative activity of the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer (SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer activity in the above cell lines at concentrations ranging from 0.01 nM to 1 microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a xenograft model of human primary colon cancer in athymic nude mice and was found to cause significant reduction in tumor volume. NMR and molecular dynamics (MD) simulation studies for this analog revealed the presence of a mixed 3(10)/alpha-helical structure. This study demonstrates that the designed BN analogs retain their anticancer activity after the incorporation of the constrained amino acid, Aib, and are potential molecules for future use in cancer therapy and drug targeting.
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PMID:Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer activity. 1703 71

The Hollow Fibre Assay (HFA) is usually applied as an early in vivo model for anti-cancer drug screening, but is potentially an excellent model for short-term in vivo pharmacodynamic studies. We used the model to study the in vivo role of thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) in the cytotoxicity and pharmacodynamics of TAS-102 in colon cancer cells. TAS-102 is a new oral drug formulation, which is composed of trifluorothymidine (TFT) and thymidine phosphorylase inhibitor (TPI), which prevents TFT degradation. We compared the activity with Xeloda (capecitabine), which is activated by TP into 5FU. Hollow fibres filled with human Colo320 or Colo320TP1 colorectal cancer cells with deficient or high TP expression, respectively, were implanted subcutaneously (s.c.) at both flanks of BALB/c mice. The mice were treated orally over 5 days with TAS-102, TFT alone, 5'DFUR+/-TPI or capecitabine at their maximum tolerated dose (MTD). The cells were retrieved from the fibres and assayed for growth (MTT assay), cell cycle distribution (flow cytometry) and apoptosis induction (FragEL method). TAS-102 induced considerable growth inhibition (50%, P<0.01) to both cell lines, which was completely abolished in the absence of TPI. Capecitabine and its metabolite 5'DFUR reduced proliferation of Colo320TP1 cells in the fibres significantly (down to 25-40%), but much less in Colo320 cells, whereas addition of TPI reduced the effect of 5'DFUR, although not completely. These differences in cytotoxic effects were reflected in the pharmacodynamic evaluation. TAS-102 induced a G2M-phase arrest (from 25 to 40%) and apoptosis (>8-fold), which was more pronounced in Colo320 than in Colo320TP1. Again, omission of TPI neutralised the effect of TAS-102. Similarly, 5'DFUR and capecitabine induced a significant G2M-phase arrest (up to 45%) in the Colo320TP1 cell line, but less pronounced in the parental Colo320. Addition of TPI to 5'DFUR reduced this effect to control levels. Also induction of apoptosis was reduced in the presence of TPI. The data demonstrated that the HFA is excellently suited for studying short-term pharmacodynamic effects of fluoropyrimidines in vivo. TAS-102 is only effective in inducing cytotoxicity when systemic TPI is present, but acts against both low and high TP expressing colon cancer cells, while 5'DFUR needs cellular TP to exert significant activity.
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PMID:The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. 1717 93

One of the significant characteristics of traditional Chinese medicine is the use of insects, other terrestrial arthropods and their products as drugs. In the present work, the extract of housefly (Musca domestica) larvae was studied by an agar well diffusion assay and minimum bactericidal concentration (MBC) determination for detection of antimicrobial activity and by MTT assay method to test its in vitro anti-tumor activity. In our studies, the extract inhibited six tested bacterial pathogens and Escherichia coli Jm109, a gene-modified strain resistant to ampicillin with the MBCs ranging from 200 to 1600 microg/ml, while Gram-positive bacteria were more sensitive than Gram-negative bacteria. The extract showed high in vitro anti-tumor activity against human colon cancer cell line CT26 with the IRs ranging from 62 to 89%. The extract of housefly larvae inoculated with Shigella dysenteriae 51302 exhibited higher antibacterial activity and in vitro anti-tumor activity than that of native larvae, which may indicate the same principle involved in the use of Bombyx mori larvae infected with silk moth fungus Beauveria bassiana and Hepialis larvae infected with Cordiceps fungus in the traditional Chinese medicine. Both extracts did not show any coagulation activity and haemolysis activity against rabbit erythrocytes at 500 and 1000 microg/ml. The results support its use in the traditional Chinese medicine, and warrant the further identification of the active molecule in the housefly larvae.
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PMID:Antibacterial activity and in vitro anti-tumor activity of the extract of the larvae of the housefly (Musca domestica). 1722

Millingtonia hortensis is an important medicinal plant in Southeast Asia, used for the treatment of asthma, sinusitis and as a cholagogue and tonic. The aim of this study was to compare the effects of aqueous and ethanol extracts of Millingtonia hortensis on the induction of apoptosis in an RKO human colon cancer cell line. Viability of RKO cells was assessed by MTT reduction assay. The aqueous extract, but not the ethanol extract of M. hortensis inhibited cell growth and proliferation in a dose- and time-dependent manner. Apoptotic cells were determined by flow cytometry and DNA fragmentation assay. Apoptotic cell numbers increased in a dose-dependent manner after treatment with aqueous extract. DNA ladders were clearly observed in RKO cells treated with 200, 300 and 400 ?g/ml of the aqueous extract of M. hortensis for 48 h. These results indicate that the aqueous extract of M. hortensis inhibited cell proliferation in an RKO colon cancer cell line via the apoptosis pathway.
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PMID:Induction of apoptosis in RKO colon cancer cell line by an aqueous extract of Millingtonia hortensis. 1725 Apr 44

The regenerating gene (REG) IV gene was isolated from a cDNA library of ulcerative colitis (UC) tissues. However, its role in the pathophysiology of UC and subsequent development of colitic cancer is still unclear. We investigated the expression of the REG IV gene in UC and colitic cancer tissues and examined whether cytokines or growth factors are responsible for REG IV gene expression and whether REG IV gene induction affects cell growth and apoptosis in colon cancer cells. The expressions of REG IV and growth factor genes in UC tissues were analyzed by real time reverse transcription-polymerase chain reaction. The effects of cytokines and growth factors on REG IV gene expression were examined in SW403 cells by Northern blot analysis. The effects of REG IV gene induction on cell growth and H(2)O(2)-induced apoptosis were examined in DLD-1 cells by MTT and TUNEL assays, respectively. REG IV mRNA was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG IV mRNA expression was correlated with that of basic fibroblast growth factor (bFGF) as well as hepatocyte growth factor (HGF) mRNA expression in UC tissues. The REG IV gene expression in SW403 colon cancer cells was enhanced by stimulation with transforming growth factor-alpha, epidermal growth factor, bFGF, and HGF. REG IV gene induction promoted cell growth and conferred resistance to H(2)O(2)-induced apoptosis in DLD-1 cells. The REG IV gene is inducible by growth factors and may function as a growth promoting and/or an antiapoptotic factor in the pathophysiology of UC.
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PMID:Expression of the REG IV gene in ulcerative colitis. 1726 7

Triptolide (TP), a traditional Chinese medicine, has been reported to be effective in the treatment of autoimmune diseases and exerting antineoplastic activity in several human tumor cell lines. This study investigates the antitumor effect of TP in human colon cancer cells (SW114) and myelocytic leukemia (K562), and elucidates the possible molecular mechanism involved. SW114 and K562 cells were treated with different doses of TP (0, 5, 10, 20, or 50 ng/ml). The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Results demonstrated that TP inhibited the proliferation of both tumor cell lines in a dose-dependent manner. To further investigate its mechanisms, the products prostaglandin E(2) (PGE(2)) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that TP strongly inhibited the production of NO and PGE(2). Consistent with these results, the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was up-regulated both at the mRNA level and the protein expression level, as shown by real-time RT-PCR and Western blotting. These results indicated that the inhibition of the inflammatory factor COX-2 and iNOS activity could be involved in the antitumor mechanisms of TP.
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PMID:Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and leukemia cells. 1727 82

The cytotoxic and antitumor activity of methanolic extract of rice hulls (MERH) were evaluated by the MTT-dye reduction assay against human colon cancer cells and the colonic aberrant crypt foci (ACF) assay in 1,2-dimethylhydrazine (DMH)-injected F344 male rats, respectively. MERH was found to be highly cytotoxic, with IC50 values of 0.5 microg/mL in vitro. Forty weeks of MERH supplementation (50 mg/kg of body weight/day) reduced colonic pre-neoplastic ACF formation by 35% (p < 0.01). An active compound, momilactone B, was isolated from MERH by silica gel chromatography, Sephadex LH-20 chromatography, and HPLC. The cytotoxic activity of momilactone B was evaluated by the MTT-dye reduction, lactate dehydrogenase (LDH), and colony-forming ability assays in human colon cancer HT-29 and SW620 cells. The results indicated that momilactone B from rice hulls might be a new candidate for chemotherapeutic agent against human colon cancer.
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PMID:Cytotoxic and antitumor activity of momilactone B from rice hulls. 1732 6

Oxaliplatin (L-OHP) is the only platinum compound to show activity in colorectal cancer. We evaluated the cytotoxicity of L-OHP on four human cancer cell lines and its influence on the cell cycle, when treated during long exposure (72 h) and different post-incubation times (24 or 72 h). We used a panel of cell lines: HT29 (colon cancer), MCF7 (breast cancer), Hela (uterine cervix) and A549 (lung adenocarcinoma). Inhibition concentration (IC)(50) was assessed by MTT assay. Cell cycle modifications were determined using dual parameter bromodeoxyuridine and propidium iodide. L-OHP yielded a superior cytotoxicity on HT29 and MCF7 relative to Hela and A549 after treatment, the post-incubations demonstrate that growth inhibition was irreversible for HT29 and Hela cell lines contrary to MCF7 and A549. The main effects of L-OHP are G2/M cell cycle arrest and transient S phase delay. Taken together, L-OHP treatment results on HT29, MCF7 and Hela, are in favor of lengthening the infusion duration to patients during further clinical trials.
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PMID:Cell cycle arrest by oxaliplatin on cancer cells. 1739 Dec 89

Recently several plant derived natural compounds have been screened for their anticancer activity in order to identify putative compounds with novel structures or mechanism of action. In the present study, fruits of Poncirus trifoliata were extracted with acetone and loaded onto silica gel column chromatography. The column was eluted with different solvents to obtain two bioactive compounds. The purity of compounds was analyzed by HPLC and their structures were identified by 1H and 13C NMR experiments as beta-sitosterol and 2-hydroxy-1,2,3-propanetricarboxylic acid 2-methyl ester (HPCME). beta-Sitosterol, HPCME, and trolox were tested for their antioxidant capacity by oxygen radical absorbance capacity (ORAC) measurement. Further, these compounds were tested for their inhibition of cancer cell proliferation and apoptosis using human colon cancer cell line (HT-29). These results were compared with the corresponding activity on non-cancerous (COS-1 fibroblast) cells. Cell proliferation and induction of apoptosis were determined by MTT assay and nuclear staining. The MTT assay indicated that both the compounds exhibited differential inhibition at various concentrations. Significant arrest of cell growth was observed with beta-sitosterol even at low concentration such as 0.63 microM in 48 h and none of the compounds exerted any apparent cytostatic effects on the non-cancerous COS-1 fibroblast cells. Growth inhibition assay suggested the potential use of bioactive compounds as cancer chemopreventive and therapeutic agents. This is the first report on HPCME isolation and identification from Rutaceae family and beta-sitosterol from P. trifoliata.
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PMID:Inhibition of colon cancer cell growth and antioxidant activity of bioactive compounds from Poncirus trifoliata (L.) Raf. 1751 44

The goal of this study was to examine the in vitro antiproliferative activity of crude methanol extracts of three traditional Korean medicinal plants: Achyranthes fauriei, Epimedium koreanum Nakai and Scutellaria baicalensis before and after heat processing. The extracts were screened for antitumoral potential by means of an MTT assay on four human cancer cell lines: lung cancer cells (Lu1), colon cancer cells (Col2), oral epidermoid carcinomas (KB) and hormone-dependent prostate cancer cells (LNCaP). None of the extracts showed significant activity against any of the cancer cell lines. However, after treatment with steam, the processed Achyranthes fauriei extract exhibited a slight, but enhanced cytotoxic activity against all four of the cancer cell lines. The processed Scutellaria baicalensis extract exerted a potent cytotoxic activity against the Lu1 cell line in a specific manner with an IC(50) value of 14.3 microg/mL. The Epimedium koreanum extract showed no cytotoxic effects against any of the cancer cell lines with or without heat processing. These results suggest that the heat processing of medicinal plants represents a possible route to the development of antitumor agents.
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PMID:In vitro cytotoxic activity of some Korean medicinal plants on human cancer cell lines: enhancement in cytotoxicity by heat processing. 1760 Aug 62


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