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)

Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase IIalpha, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.
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PMID:Mithramycin inhibits etoposide resistance in glucose-deprived HT-29 human colon carcinoma cells. 1809 71

We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating multiple drug-resistant colon cancers.
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PMID:Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines. 1818 4

The fully ripened fruit of Katsura-uri Japanese pickling melon ( Cucumis melo var. conomon) has rarely been used for food because the midripened fruit is utilized for making pickles, but the fully ripened fruit is no longer valuable for pickles due to the fruit body being too soft. We have considered the utilization of the fully ripened Katsura-uri fruit that may be used for nonpickling products, particularly if the fully ripened fruit demonstrated health benefits such as anticarcinogenic properties. The phytochemical extract from the fully ripened fruit of Katsura-uri Japanese pickling melon was purified via a bioassay-guided fractionation scheme, which was based on the induction of differentiation in a RCM-1 human colon cancer cell line. On the criteria of two differentiation markers (duct formation and alkaline phosphatase activity), the most potent fraction contained a compound identified as 3-methylthiopropionic acid ethyl ester, based on GC retention time, EI-MS, (1)H NMR, and (13)C NMR spectra. Previously, the role of 3-methylthiopropionic acid ethyl ester was considered as an odor producing compound in many fruits, but this study indicates potential medical benefits of this compound.
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PMID:3-Methylthiopropionic acid ethyl ester, isolated from Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon), enhanced differentiation in human colon cancer cells. 1842 16

Potential cancer preventive constituents of sour orange (Citrus aurantium L.) were isolated and identified from EtOAc extract of sour orange. Crude EtOAc extract was purified using silica gel column chromatography to isolate two putative bioactive compounds. The purity of the isolated compounds was analyzed by TLC and HPLC. The structures of the two compounds were identified by one-dimensional ((1)H, (13)C) and two-dimensional ((1)H-H and (1)H-(13)C) NMR experiments as isolimonic acid and a novel compound named as ichanexic acid. Stereochemical assignment of the protons for both the compounds was made using one-dimensional nuclear Overhauser enhancement (nOe) experiments. The identified compounds were tested for the inhibition of human colon cancer cells (HT-29) proliferation, apoptosis, and on non-cancerous (COS-1 fibroblast) cells. Cell proliferation, arrest of cell growth, and induction of apoptosis were determined by MTT assay, flow cytometry, and nuclear staining methods, respectively. The MTT assay indicated that both the compounds exhibited differential inhibition at various concentrations. Significant arrest of cell growth by isolimonoic acid was noticed within 24h of treatment on the HT-29 colon cancer cells at a concentration as low as 5.0microM (P=0.005) and by ichanexic acid at 10.0microM (P=0.011). None of the compounds exerted any apparent cytostatic effects on the non-cancerous COS-1 fibroblast cells. Both the compounds exerted nearly 4- to 5-fold increase in the counts of G2/M stage cells at 5microM indicating a potential role in the cell cycle arrest as well as possible lead structures for the development of cancer chemopreventive and therapeutic agents. To the best of our knowledge, this is the first report on isolation, identification of isolimonic acid in its native form, and compound 2 was found to a novel and identified as ichanexic acid.
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PMID:Novel triterpenoid from Citrus aurantium L. possesses chemopreventive properties against human colon cancer cells. 1849 Jan 69

Intrinsically disordered proteins are emerging as substantial functional constituents of mammalian proteomes. Although the abundance of these proteins has been established by bioinformatics approaches, the vast majority have not been characterized structurally or functionally. The C/EBP homologous protein (CHOP) is a proto-oncogene, traditionally shown as a dominant-negative inhibitor of C/EBPs and a transcriptional activator of activating protein-1. We report here the in vitro characterization of CHOP, where our computational analyses and experimental evidences show for the first time that CHOP is an intrinsically disordered protein. Intrinsic fluorescence, NMR spectroscopy, and analytical size-exclusion chromatography studies indicate that CHOP contains extensive disordered regions and self-associate in solution. Interestingly, the disordered N-terminal region has a key role in the oligomerization of CHOP and is vital for its biological activity. We report a novel mechanistic role of CHOP in the inhibition of Wnt/TCF signaling and stimulation of c-Jun and sucrase-isomaltase reporter activity in intestinal colon cancer cells. These findings are discussed in the context of oligomerization of intrinsically disordered proteins as one of the mechanisms through which they exert their biological function.
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PMID:Intrinsically disordered human C/EBP homologous protein regulates biological activity of colon cancer cells during calcium stress. 1853 16

Bis-sesquiterpenes, henriols A (1), B (2), C (3), and D (4), and three diterpenes, henrilabdanes A (5), B (6), and C (7), together with two known bis-sesquiterpenes and three known labdane diterpenes, were isolated from the ethanol extract of the roots of Chloranthus henryi. Their structures and absolute configurations were elucidated by NMR spectroscopic, X-ray crystallographic and CD analyses. Compounds 1, 5, 6 and 7 showed moderate hepatoprotective activities with IC(50) values of 0.19, 0.66, 0.09 and 0.18 microM, respectively. They were not studied further due to the weak effects noted. Compounds 3 and 8 exhibited cytotoxic activities against three types of cancer cell lines including the hepatoma (BEL-7402), human gastric carcinoma (BGC-823), and colon cancer (HCT-8).
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PMID:Bis-sesquiterpenes and diterpenes from Chloranthus henryi. 1892 75

To examine the anticancer activity several novel thiazolone-based compounds containing 5-aryl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl framework were obtained. Reaction of 5-aryl-3-phenyl-4,5-dihydropyrazole with 4-thioxo-2-thiazolidinone or 2-carbethoxymethylthio-2-thiazoline-4-one yielded starting 4- (1 and 2) or 2-substituted (11 and 12) thiazolones which were utilized in Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 3-10, 13-18. Alternatively 11, 12 and their 5-arylidene derivatives were synthesized by means of 3-phenyl-5-aryl-1-thiocarbamoyl-2-pyrazoline as S,N-binucleophile via [2+3]-cyclocondensation approach. The structures of compounds were determined by (1)H, (13)C NMR, LC-MS, EI-MS and X-ray analysis. The in vitro anticancer activity of synthesized compounds were tested by the National Cancer Institute and most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines. Relations between structure and activity are discussed, the most efficient anticancer compound 16 was found to be active with selective influence on colon cancer cell lines, especially on HT 29 (logGI(50)=-6.37).
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PMID:Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. 1900 Jun 43

Allium leucanthum C. Koch is an endemic Caucasian species that grows in Georgia. The flowers are used in traditional medicine. Phytochemical investigation allowed the isolation of seven spirostanol type saponins from the flowers. Their structures were elucidated on the base of NMR and HRESIMS spectrometry data. A new compound, which we have named leucospiroside A (5), has been identified as (25R)-5alpha-spirostane-2alpha,3beta,6beta-triol 3-O-beta-glucopyranosyl-(1-->3)-beta-glucopyranosyl-(1-->2)-[beta-glucopyranosyl-(1-->3)]-beta-glucopyranosyl-(1-->4)-beta-galactopyranoside. The six others were known substances, but are described in this plant for the first time. The crude extract, spirostanol and furostanol fractions, as well as isolated compounds, were evaluated for their in vitro cytotoxic activity. Compounds 1-3 and 5 were found to be the most active, with relatively similar IC50 values ranging from 3.7 to 5.8 microM for a lung cancer cell line (A549) and 5.6 to 8.2 microM for a colon cancer cell line (DLD-1).
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PMID:Cytotoxic steroidal saponins from the flowers of Allium leucanthum. 1903 84

A benzil, calophione A, 1-(6'-Hydroxy-1',3'-benzodioxol-5'-yl)-2-(6''-hydroxy-2''-isopropenyl-2'',3''-dihydro-benzofuran-5''-yl)-ethane-1,2-dione and three coumestan derivatives, tephcalostan B, C and D were isolated from the roots of Tephrosia calophylla. Their structures were deduced from spectroscopic data, including 2D NMR (1)H-(1)H COSY and (13)C-(1)H COSY experiments. Compounds were evaluated for cytotoxicity against RAW (mouse macrophage cells) and HT-29 (colon cancer cells) cancer cell lines and antiprotozoal activity against various parasitic protozoa. Calophione A exhibited significant cytotoxicity with IC(50) of 5.00 (RAW) and 2.90microM (HT-29), respectively.
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PMID:Cytotoxic benzil and coumestan derivatives from Tephrosia calophylla. 1906 50

Novel complexes of platinum(II) with 3- (1) or 4-acetylpyridine (2) have been synthesized and characterized by elemental analyses, IR, (1)H and (13)C NMR spectroscopy. Single crystal X-ray diffraction revealed the trans geometry of complex 2. DFT calculations confirm formation of trans isomers for both complexes. The complexes have been tested for their cytotoxicity against HeLa (human cervical cancer), U2OS (human osteosarcoma), U2OScisR (human osteosarcoma cisplatin resistant), B16 (murine melanoma), MDA-453, MDA-361, and MCF-7 (human breast cancer), LS-174 (human colon cancer) and FemX (human melanoma) cell lines. The most promising compound trans-dichloridobis(4-acetylpyridine)platinum(II) (2) overcomes cisplatin resistance of U2OScisR cells after 48h of drug exposure.
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PMID:Novel trans-dichloridoplatinum(II) complexes with 3- and 4-acetylpyridine: Synthesis, characterization, DFT calculations and cytotoxicity. 1907 Sep 43


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