Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
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Antioxidant-guided fractionation of Mammea americana L. seeds resulted in the identification of three new isoprenylated coumarins, mammea B/BA hydroxycyclo F (1), mammea E/BC (2), and mammea E/BD (3). In addition, twelve known isoprenylated coumarins, mammea A/AA (4), mammea A/AA cyclo D (5), mammea A/AA cyclo F (6), mammea A/AC cyclo D (7), mammea A/AD cyclo D (8), mammea B/BA (9), mammea B/BA cyclo F (10), mammea B/BB (11), mammea B/BC (12), mammea B/BD (13), mammea E/BA (14), and mammea E/BB (15), as well as two known flavanols, (+)-catechin (16) and (-)-epicatechin (17) were identified. The fifteen isoprenylated coumarins were screened for their cytotoxicity in the SW-480, HT-29, and HCT-116 human colon cancer cell lines and antioxidant capacities in the DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical assay. Compounds 1 - 15 exhibited significant cytotoxic activities in the SW-480, HT-29, and HCT-116 human colon cancer cell lines (IC50 ranges 13.9 - 88.1, 11.2 - 85.3, and 10.7 - 76.7 microM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 microM), a drug frequently used for human colon cancer treatment. Compounds 2 - 4, 9, and 11 - 15 displayed high antioxidant activity in the DPPH assay (IC50 range 86 - 135 microM), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 microg/mL) in the DPPH assay. The results of these assays were used to study the structure-activity relationships for this class of compounds. In the SW-480 cell line, the three new coumarins, 1 - 3, also exhibited dose-dependent increases in sub-diploid cells by flow cytometry, indicating that they induce apoptosis.
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PMID:Antioxidant and cytotoxic isoprenylated coumarins from Mammea americana. 1620 41

Incubation with 5-n-alkylresorcinols (chain lengths C15:0, C17:0, C19:0, C21:0, and C23:0) increased the self-protection capacity of HT29 human colon cancer cells against DNA damage induced by hydrogen peroxide and genotoxic fecal water samples using comet assay (single-cell gel electrophoresis assay). The alkylresorcinols did not exert potent antioxidant activity in the FRAP (ferric reduction ability of plasma) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical assays. However they were able to significantly inhibit copper-mediated oxidation of human LDL (low-density lipoprotein) in vitro, and pentadecylresorcinol at 25 micromol/L increased lag time by 65 min. The results show that alkylresorcinols have antigenotoxic and antioxidant activity under in vitro conditions.
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PMID:In vitro antioxidant activity and antigenotoxicity of 5-n-alkylresorcinols. 1650 14

The potential antiproliferative and antiradical activities of an enzymatic extract of Ecklonia cava together with its crude polysaccharide (CpoF) and crude polyphenolic fractions (CphF) were evaluated in vitro. Tested extracts showed strong selective cell proliferation inhibition on all cancer cell lines tested, especially CphF extract, containing high polyphenol amount, showed 5.1 microg/ml of IC(50) value on murine colon cancer (CT-26) cell line. According to the nuclear staining experiment, antiproliferative effect of CphF was associated with apoptotic cell demise in CT-26. In addition, The CphF at 5 microg/ml scavenged 70% of DPPH radical, which is much higher than those of BHA and BHT at same concentration. Further more CphF exhibited interesting antiradical properties, expressed by its capacity to scavenge superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH()). In reducing power assay, CphF extract at 5 microg/ml was found to be as high as that of BHT at same concentration. Also, in total antioxidant assay the effect of CphF at 50 microg/ml was equivalent or slightly higher than those of commercial counterparts at 5 microg/ml concentration. Taken together, the CphF may be a promising alternative to synthetic substances as natural compound with high antiproliferative and antiradical activity.
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PMID:Antiproliferative and antioxidant properties of an enzymatic hydrolysate from brown alga, Ecklonia cava. 1651 67

Seed flours from black raspberry, red raspberry, blueberry, cranberry, pinot noir grape, and chardonnay grape were examined for their total fat content, fatty acid composition, total phenolic content (TPC), total anthocyanin content (TAC), radical scavenging capacities against the peroxyl (ORAC) and stable DPPH radicals, chelating capacity against Fe(2+), and antiproliferative activities using the HT-29 colon cancer cell line. Significant levels of fat were detected in the fruit seed flours and their fatty acid profiles may differ from those of the respective seed oils. Cranberry seed flour had the highest level of alpha-linolenic acid (30.9 g/100 g fat) and the lowest ratio of n-6/n-3 fatty acids (1.2/1). The ORAC value of the chardonnay seed flour was 1076.4 Trolox equivalents mumol/g flour, and its TPC was 186.3 mg gallic acid equivalents/g flour. These values were 3-12 times higher than the other tested fruit seed flours. Furthermore, the ORAC value was significantly correlated to the TPC under the experimental conditions (P < 0.05). These fruit seed flours also differed in their TAC values and Fe(2+)-chelating capacities. In addition, black raspberry, cranberry, and chardonnay grape seed flour extracts were evaluated for their antiproliferative effects using HT-29 colon cancer cells. All three tested seed flour extracts significant inhibited HT-29 cell proliferation. The data from this study suggest the potential of developing the value-added use of these fruit seed flours as dietary sources of natural antioxidants and antiproliferative agents for optimal human health.
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PMID:Chemical compositions, antioxidant capacities, and antiproliferative activities of selected fruit seed flours. 1671 95

Several natural antimicrobial compounds derived from essential oils of plants were investigated for their efficacies in inhibiting decay and extending the shelf life of strawberries (Fragaria x ananassas Duch.). The severity of decay in strawberries stored at 10 degrees C was significantly reduced by treatment with thymol. Treatments with menthol or eugenol also suppressed the fungal growth, but to a lesser extent. All of these three natural antimicrobial compounds extended shelf life of strawberries as compared to the control. Strawberries treated with thymol, menthol, or eugenol also maintained better fruit quality with higher levels of sugars, organic acids, phenolics, anthocyanins, flavonoids, and oxygen radical absorbance capacity than the untreated fruits. The free radical scavenging properties of strawberry fruit were evaluated against 2,2-diphenyl-1-picryhydrazyl (DPPH(.)), hydroxyl (HO(.)), and superoxide radicals (O2(.-)) using electron spin resonance measurements. Higher radical scavenging capacities were found against DPPH(.) and HO(.) in all treated fruit, particularly in berries treated with thymol, compared to those in the control groups. In addition, strawberry extracts were evaluated for their antiproliferative activities using HT-29 colon cancer cells. Extracts from all treated fruit exhibited significantly stronger inhibition on HT-29 cell proliferation than those from the control fruit. These data provide evidence that, in addition to possessing antimicrobial activity, the essential oils also increase free radical scavenging capacity and antiproliferative activity in fruit and, in turn, enhance the resistance of fruit tissues to deterioration and spoilage.
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PMID:Enhancing antioxidant, antiproliferation, and free radical scavenging activities in strawberries with essential oils. 1763 36

The medicinal mushroom Inonotus obliquus is a traditional and widely used multi-functional fungus. Hot water (50 degrees C, 70 degrees C, and 80 degrees C) and ethanol crude extracts of I. obliquus were investigated for their antioxidant activity with superoxide dismutase (SOD) and (1,1-diphenyl-2-picryhydrazyl) (DPPH) radical-scavenging activity assays. We also investigated the antiproliferative effects and ability of the extracts to induce apoptosis in human colon cancer DLD-1 cells. Among the four extracts, the ethanol extract (EE) exhibited the strongest SOD-like activity and antiproliferative effect on DLD-1 cells, and exposure to the EE resulted in the induction of apoptosis, whereas no apoptosis was observed in DLD-1 cells exposed to the hot water extracts (HWEs). HWE at 70 degrees C (HWE70) exhibited the strongest DPPH radical-scavenging activity (EC50, 126 microg/ml), whereas the EE showed the weakest activity (EC50, 224 microg/ml). The different biological activities among the four extracts may be attributed to differences in their chemical composition, partially supported by polysaccharide, protein and phenolic content, and the 1H-NMR spectra.
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PMID:Comparative study of antioxidant activity and antiproliferative effect of hot water and ethanol extracts from the mushroom Inonotus obliquus. 1914 8

DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing susceptibility to chronic disease. While structure-activity relationships have provided guidelines on molecular structure in relation to free hydroxyl-radical scavenging, this may not cover the situation in food plants where the anthocyanins are part of a complex mixture, and may be part of complex structures, including anthocyanic vacuolar inclusions (AVIs). Additionally, new analytical methods have revealed new structures in previously-studied materials. We have compared the antioxidant activities of extracts from six anthocyanin-rich edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato skin, purple sweetpotato flesh and Maori potato flesh) using three chemical assays (DPPH, TRAP and ORAC), and the in vitro Comet assay. Extracts from the flowering plant, lisianthus, were used for comparison. The extracts showed differential effects in the chemical assays, suggesting that closely related structures have different affinities to scavenge different reactive species. Integration of anthocyanins to an AVI led to more sustained radical scavenging activity as compared with the free anthocyanin. All but the red lettuce extract could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while extracts from purple sweetpotato skin and flesh, Maori potato and pansies, protected cells against subsequent challenge by hydrogen peroxide at 0 degrees C, red cabbage extracts were pro-oxidant, while other extracts had no effect. When the peroxide challenge was at 37 degrees C, all of the extracts appeared pro-oxidant. Maori potato extract, consistently the weakest antioxidant in all the chemical assays, was more effective in the Comet assays. These results highlight the dangers of generalising to potential health benefits, based solely on identification of high anthocyanic content in plants, results of a single antioxidant assay and traditional approaches to structure activity relationships. Subsequent studies might usefully consider complex mixtures and a battery of assays.
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PMID:Dietary protection against free radicals: a case for multiple testing to establish structure-activity relationships for antioxidant potential of anthocyanic plant species. 1939 39

The novel urea primaquine derivatives 3 were prepared by aminolysis of primaquine benzotriazolide 2 with several hydroxyamines and ethylendiamine, while carbamates 4 were synthesized from the same precursor 2 and alcohols. All compounds are fully chemically characterized and evaluated for their cytostatic and antioxidant activities. The most prominent antiproliferative activity was obtained by compounds 3c, 3d, 3g, and 5b (IC(50)=9-40 microM). 1-(5-Hydroxypentyl)-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]urea (3c) showed extreme selectivity toward SW 620 colon cancer cells (IC(50)=0.2 microM) and a bit less toward lung cancer cells H 460. Hydroxyurea 3h showed the highest interaction with DPPH. Primaquine twin drug 3g showed very significant inhibition on LOX soybean (IC(50)=62 microM). Almost all the tested derivatives highly inhibited lipid peroxidation, significantly stronger than primaquine phosphate.
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PMID:Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities. 1958 Oct 98

Some tuber-bearing wild potato species are reportedly higher in potential health-promoting traits, such as antioxidant activity (AOA) and total phenolic content (TP), than commercial cultivars; therefore, they could be used as parental material in breeding for high AOA and TP. However, using wild species might result in progenies that are toxic for human consumption because of the presence of high total glycoalkaloids (TGAs) and other unknown compounds. Therefore, wild potato accessions should be screened for cytotoxicity before their introduction into breeding programs. The objective of this study was to investigate antiproliferative activity and cytotoxicity of tuber extracts from 15 Solanum jamesii accessions on human HT-29 colon and LNCaP prostate cancer cell lines in vitro. Also, correlations among AOA, TP, TGA, and antiproliferative activity were determined. The tuber extracts significantly inhibited proliferation of HT-29 and LNCaP cell lines and were not cytotoxic to the cells compared to the control (DMSO). The antiproliferative activity exhibited by tuber extracts was not due to necrosis, because the amount of lactate dehydrogenase (LDH) released from cells incubated with the extracts was not significantly different from that released from cells incubated without extracts (control). Colon cancer cells were more responsive to tuber extract treatment than prostate cancer cells. In both HT-29 and LNCaP cells, there were no observable significant correlations between antioxidant activity (DPPH and ABTS) and inhibition of cell proliferation or between TP and cell proliferation inhibition. Also, glycoalkaloids did not exhibit significant correlations with the inhibition of cancer cell proliferation. Findings of this study show that S. jamesii accessions probably pose no cytotoxic effects when used as parental material in improving the nutritional value of potato cultivars. Correlation results, along with cell proliferation data, suggest that not only the compounds measured in this study but also other bioactive compounds present in the matrix acting additively or synergistically may be more responsible for the antiproliferative effects of potato tuber extracts than higher concentrations of a single or group of compounds.
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PMID:Antiproliferative activity and cytotoxicity of Solanum jamesii tuber extracts on human colon and prostate cancer cells in vitro. 1971 17

Phenolic compounds, namely, hydrolyzable tannins and low molecular weight phenolic compounds, were isolated and purified from Portuguese cork from Quercus suber L. Some of these compounds were studied to evaluate their antioxidant activity, including free-radical scavenging capacity (DPPH method) and reducing capacity (FRAP method). All compounds tested showed significant antioxidant activity, namely, antiradical and reducing properties. The antiradical capacity seemed to increase with the presence of galloyl groups. Regarding the reducing capacity, this structure-activity relationship was not so clear. These compounds were also studied to evaluate the growth inhibitory effect on the estrogen responsive human breast cancer cell line (ER+) MCF-7 and two other colon cancer cell lines (Caco-2 and HT-29). Generally, all the compounds tested exhibited, after a continuous exposure during a 48 h period, a dose-dependent growth inhibitory effect. Relative inhibitory activity was primarily related to the number of phenolic hydroxyl groups (galloyl and HHDP moieties) found in the active structures, with more groups generally conferring increased effects, except for HHDP-di-galloyl-glucose. Mongolicain B showed a greater potential to inhibit the growth of the three cell lines tested, identical to the effect observed with castalagin. Since these compounds are structurally related with each other, this activity might be based within the C-glycosidic ellagitannin moiety.
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PMID:Antioxidant and biological properties of bioactive phenolic compounds from Quercus suber L. 1988 28


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