Evaluation of allelopathic potential and quantification of momilactone A,B from rice hull extracts and assessment of inhibitory bioactivity on paddy field weeds

Rice (Oryza sativa L.) hull extracts were used in a bioassay to evaluate the allelopathic potential of rice on the germination and growth of barnyard grass (Echinochloa crus-galli P. Beauv. var. oryzicola Ohwi), to quantify momilactone A and B levels in rice hull germplasm and to assess the inhibitory bioactivity of momilactone A and B as a potential natural source of herbicide for weed control in paddy fields. Four varieties of weeds including E. crus-galli P. Beauv. var. oryzicola Ohwi, Monochoria vaginalis var. plantaginea, Scirpus juncoides, and Eleocharis kuroguwai were tested in the paddy field. Of 99 rice varieties, the top five including Noindari exhibited inhibition effects greater than 50% in average inhibition of dry weight (AIDW). Noindari among them exerted the strongest effect (55.6%). The next five in the ranking exhibited inhibition effects of greater than 40%. Also, 46 varieties had inhibition effects between 20 and 40%, and 29 varieties had inhibition effects greater than 10%. Fourteen varieties had very low inhibitory effects (less than 10%), the lowest of which was Heunbe (4.7%). These varieties showed a mean inhibition of 19.8% for germination rate (GR), 9.9% for germination percentage (GP), 16.6% for leaf dry weight (LDW), 38.9% for straw dry weight (SDW), and 26.8% for root dry weight (RDW). Rice varieties were classified into six categories based on their total momilactones (TMs) (momilactone A + momilactone B). The highest level of momilactone A was found in the Baekna rice variety (34.7 microg g(-1)), and Baekgwangok contained the highest level of momilactone B (37.8 microg g(-1)). In allelopathic potential with genetic properties and morphological characteristics, the total inhibition rate (TIR) was 18.3% for Korean rice varieties, 19.0% for middle maturing varieties, 17.8% for colorless hull varieties, 18.3% for awn varieties, and 19.0% for colorless awn varieties. In addition, Korean varieties showed higher TMs (4.5 microg g(-1)) as compared with varieties that were late maturing (4.4 microg g(-1)), had colorless hulls (4.1 microg g(-1)), awns (4.7 microg g(-1)), and colorless awns (4.8 microg g(-1)). Momilactone A levels were generally higher than momilactone B levels. Total inhibition rates on barnyard grass correlated with average inhibitions of germination (AIG) (r2 = 0.62***), AIDW (r2 = 0.92***), and were affected by the inhibition rate of GP (r2 = 0.57***). Regions of origin for rice varieties correlated with the AIG (r2 = -0.23***), and maturing time showed a positive correlation with SDW (r2 = 0.15**) and RDW (r2 = 0.19**). Levels of momilactones were also correlated with the region of origin (r2 = -0.32***), maturing time (r2 = 0.13***), and awns (momilactone A, r2 = 0.23***; momilactone B, r2 = 0.14**), suggesting that rice varieties with awns, Korean varieties, and varieties with later maturing times contain higher levels of momilactone. Also, the investigation of the momilactone A and B bioactivity (0, 250, 500, 1000, 2000, and 4000 g a.i./ha) for weed control in paddy fields indicated that momilactones A and B exhibited no toxicity (0 in all concentrations) against rice plants, and the inhibitory bioactivity on weeds with momilactone A was higher than that of momilactone B. When compared with no momilactone control, the highest inhibitory effect (50%) on E. crus-galli P. Beauv. var. oryzicola Ohwi was shown on the 14th day after the application of momiactone A. The inhibitory effect increased with the concentration of the compound from 250 to 4000 g a.i./ha. Furthermore, momilactone A showed greater suppression than momliactone B toward toward E. crus-galli P. Beauv. var. oryzicola Ohwi, M. vaginalis var. plantaginea, S. juncoides, and E. kuroguwai. In broad weed species, momilactone A showed the highest inhibitory effect (90% in 4000 g a.i./ha) on S. juncoides, 14 days after the application as compared with no momilactone control. Further studies on allelopathic effects and momilactones from the germplasm of rice varieties using genetic properties and morphological characteristics may facilitate the development of rice varieties with higher allelopathic potential. Momilactones A and B present in rice hulls may serve as a potential natural herbicide source for weed control in paddy fields reducing the dependence on synthetic herbicides.     

Probiotics prevent the development of 1,2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages

Probiotics modulate immunity and inhibit colon carcinogenesis in experimental models, but these effects largely depend on the bacterial strain, and the precise mechanisms are not well understood. Therefore, we studied the effect of Bifidobacterium longum and/or Lactobacillus gasseri on the development of 1,2-dimethylhydrazine (DMH)-induced colonic precancerous lesions and tumors in mice while delineating the possible mechanisms involved. The results suggest that dietary consumption of probiotics (B. longum and L. gasseri) resulted in a significant inhibition of DMH-induced aberrant crypt foci (ACF) formation in male ICR mice. Long-term (24 weeks) dietary consumption of probiotics resulted in a reduction of colon tumor multiplicity and the size of the tumors. Administration of B. longum and L. gasseri suppressed the rate of colonic mucosa cellular proliferation in a manner correlating with the inhibition of tumor induction by DMH. In addition, the phagocytic activity of peritoneal macrophages was significantly increased in the DMH-treated mice that were fed various doses of B. longum, but not with L. gasseri or combined probiotics (B. longum + L. gasseri). We also found that L. gasseri significantly increased the proliferation of RAW264.7 macrophage cells through an increase in S phase DNA synthesis, which was related to the up-regulation of proliferating cell nuclear antigen (PCNA) and cyclin A. Taken together, these results demonstrate the in vivo chemopreventive efficacy and the immune stimulating mechanisms of dietary probiotics against DMH-induced colonic tumorigenesis.     

Resveratrol oligomers isolated from Carex species inhibit growth of human colon tumorigenic cells mediated by cell cycle arrest

Research has shown that members of the Carex genus produce biologically active stilbenoids including resveratrol oligomers. This is of great interest to the nutraceutical industry given that resveratrol, a constituent of grape and red wine, has attracted immense research attention due to its potential human health benefits. In the current study, five resveratrol oligomers (isolated from Carex folliculata and Carex gynandra ), along with resveratrol, were evaluated for antiproliferative effects against human colon cancer (HCT-116, HT-29, Caco-2) and normal human colon (CCD-18Co) cells. The resveratrol oligomers included one dimer, two trimers, and two tetramers: pallidol (1); α-viniferin (2) and trans-miyabenol C (3); and kobophenols A (4) and B (5), respectively. Although not cytotoxic, the resveratrol oligomers (1-5), as well as resveratrol, inhibited growth of the human colon cancer cells. Among the six stilbenoids, α-viniferin (2) was most active against the colon cancer cells with IC(50) values of 6-32 μM (>2-fold compared to normal colon cells). Moreover, α-viniferin (at 20 μM) did not induce apoptosis but arrested cell cycle (in the S-phase) for the colon cancer but not the normal colon cells. This study adds to the growing body of knowledge supporting the anticancer effects of resveratrol and its oligomers. Furthermore, Carex species should be investigated for their nutraceutical potential given that they produce biologically active stilbenoids such as α-viniferin.     

Identification of a novel cytotoxic protein, Cry45Aa, from Bacillus thuringiensis A1470 and its selective cytotoxic activity against various mammalian cell lines

Parasporal inclusion proteins produced by Bacillus thuringiensis strain A1470 exhibit strong cytotoxicity against human leukemic T cells when activated by protease treatment. One of the cytotoxic proteins was separated by anion exchange chromatography and gel filtration chromatography and designated Cry45Aa. Its gene was then expressed in recombinant Escherichia coli, in which the Cry45Aa precursor was accumulated in an inclusion body. It was solubilized in sodium carbonate buffer and processed with proteinase K, and cytotoxic activities of the protein against various mammalian cell lines were evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assay. The protein exhibited high cytotoxic activity against CACO-2, Sawano, MOLT-4, TCS, and HL60 cells and moderate activity against U-937 DE-4, PC12, and HepG2 cells. On the other hand, the EC50 values against Jurkat, K562, HeLa, A549, Vero, COS-7, NIH3T3, CHO, and four normal tissue cells (human primary hepatocyte cells, UtSMC, MRC-5, and normal T cells) were >2 microg/mL.     

Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth

Commercially prepared grape (Vitis vinifera), bilberry (Vaccinium myrtillus L.), and chokeberry (Aronia meloncarpa E.) anthocyanin-rich extracts (AREs) were investigated for their potential chemopreventive activity against colon cancer. The growth of colon-cancer-derived HT-29 and nontumorigenic colonic NCM460 cells exposed to semipurified AREs (10-75 microg of monomeric anthocyanin/mL) was monitored for up to 72 h using a sulforhodamine B assay. All extracts inhibited the growth of HT-29 cells, with chokeberry ARE being the most potent inhibitor. HT-29 cell growth was inhibited approximately 50% after 48 h of exposure to 25 microg/mL chokeberry ARE. Most importantly, the growth of NCM460 cells was not inhibited at lower concentrations of all three AREs, illustrating greater growth inhibition of colon cancer, as compared to nontumorigenic colon cells. Extracts were semipurified and characterized by high-pressure liquid chromatography, spectrophotometry, and colorimetry. Grape anthocyanins were the glucosylated derivatives of five different anthocyanidin molecules, with or without p-coumaric acid acylation. Bilberry contained five different anthocyanidins glycosylated with galactose, glucose, and arabinose. Chokeberry anthocyanins were cyanidin derivatives, monoglycosylated mostly with galactose and arabinose. The varying compositions and degrees of growth inhibition suggest that the anthocyanin chemical structure may play an important role in the growth inhibitory activity of commercially available AREs.     

Changes in Water Absorption and Swollen Volume in Extruded Alkaline Peroxide Pretreated Rice Hulls

Rice hulls were pretreated with an alkaline (pH 11.5) solution of hydrogen peroxide (1%) and then extruded. Pretreatment of rice hulls (4% db) at 50°C for 12 hr promoted 94.4% silica reduction, caused lignin solubilization and increased water absorption index (54%) and swollen volume (44%). The effects of temperature (125, 175, and 225°C), moisture content (25, 30, and 35%) and screw speed (120, 140, and 160 rpm) on water absorption and swollen volume of rice hulls fiber were evaluated after extrusion in a single-screw extruder. Operational conditions that produced the most modified product with regard to the functional properties were: 125°C, 35% moisture, and 120 rpm. Extruded fiber had a water absorption index 95% higher and swollen volume 138% higher than the unprocessed material. Microscopic examination showed a slight effect on the hulls epidermis after pretreatment, while extrusion promoted cellular structure disruption.     

Peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) potently suppresses dextran sulfate sodium-induced colitis and colon tumorigenesis in mice

Previous studies reported that peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) has antiproliferative and anti-inflammatory activities. Here, we evaluated the chemopreventive effects and underlying molecular mechanisms of dietary administration of AcEGCG and EGCG in dextran sulfate sodium (DSS)-induced colitis in mice. The mice were fed a diet supplemented with either AcEGCG or EGCG prior to DSS induction. Our results indicated that AcEGCG administration was more effective than EGCG in preventing the shortening of colon length and the formation of aberrant crypt foci (ACF) and lymphoid nodules (LN) in mouse colon stimulated by DSS. Our study observes that AcEGCG treatment inhibited histone 3 lysine 9 (H3K9) acetylation but did not affect histone acetyltransferase (HAT) activity and acetyl- CREB-binding protein (CBP)/p300 levels. In addition, pretreatment with AcEGCG decreased the proinflammatory mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation and p65 acetylation. We also found that treatment with AcEGCG increased heme oxygenase-1(HO-1) expression via activation of extracellular signal-regulated protein kinase (ERK)1/2 signaling and acetylation of NF-E2-related factor 2 (Nrf2), thereby abating DSS-induced colitis. Moreover, dietary feeding with AcEGCG markedly reduced colitis-driven colon cancer in mice. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary AcEGCG against inflammatory bowel disease (IBD) and potentially colon cancer associated with colitis. These findings provide insight into the biological actions of AcEGCG and might establish a molecular basis for the development of new cancer chemopreventive agents.     

Structures of new triterpenoids and cytotoxicity activities of the isolated major compounds from the fruit of Momordica charantia L

Two new cucurbitane-type triterpene glycosides, charantagenins D (1) and E (2), and one new sterol, 7-oxo-stigmasta-5,25-diene-3-O-β-d-glucopyranoside (3), were isolated from the fruit of Momordica charantia L. together with another eight known compounds. Their structures were determined on the basis of spectral analysis. Cytotoxicity activities of the isolated major compounds were evaluated against lung cancer cell line A549, glioblastoma cell line U87, and hepatoma carcinoma cell line Hep3B by using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in vitro assay. Results showed compounds 1 and 7 (goyaglycoside d) with an -OMe substituent group in the side chain exhibited significant cytotoxic activities against cancer cells. Impressively, the IC(50) values of the new compound 1 to A549, U87, and Hep3B were 1.07, 1.08, and 14.01 μmol/L, respectively, which were much lower than those of other tested compounds.     

o-Orsellinaldehyde from the submerged culture of the edible mushroom Grifola frondosa exhibits selective cytotoxic effect against Hep 3B cells through apoptosis

The tumoricidal activity of a bioactive metabolite produced by submerged culture in a 2.1-L airlift fermentor of Grifola frondosa NTUS was investigated. After 14 days of cultivation, ethyl acetate extracts from the supernatant of culture broth (EES) were analyzed by cell viability assay. The IC50 of EES for cytotoxicity against human carcinoma cells (Hep 3B, Hep G2, HeLa, CL1-1) and normal human lung fibroblast MRC-5 was 78.4, 52.7, 77.6, 71.0, and 233.3 microg/mL, respectively. EES was further fractionated and a main cytotoxic compound, HE-5-5, was obtained. The IC50 of HE-5-5 based on the cell viability of Hep 3B and MRC-5 cells was 3.6 and 33.1 microg/mL, respectively. Thus, HE-5-5 showed a selective cytotoxic effect against Hep 3B cells and MRC-5. According to the UV, MS, and NMR data, HE-5-5 was identified as o-orsellinaldehyde. A DNA fragmentation assay together with the presence of a significant sub-G1 peak by flow cytometry suggested that o-orsellinaldehyde might mediate its cytotoxicity through apoptosis.     

Effects of black soybean [Glycine max (L.) Merr.] seed coats and its anthocyanidins on colonic inflammation and cell proliferation in vitro and in vivo

Anti-inflammatory and antiproliferative activities of anthocyanidins and anthocyanin-rich black soybean seed coats were studied in HT-29 human colon adenocarcinoma cells and carcinogen-treated F344 rats, respectively. Cyanidin and delphinidin significantly inhibited cell growth at concentrations of >or=1 microM. Anthocyanidins suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNAs in TPA-stimulated HT-29 cells. Both yellow and black soybean seed coat supplementation (10%, w/w) did not significantly reduce the number of aberrant crypt foci (ACF), although a modest decrease in the number of ACF was observed in animals fed soybean seed coats. The colonic COX-2 mRNA level was suppressed in rats fed both soybean seed coat diet. The plasma prostaglandin E 2 (PGE 2) level was reduced only in rats fed black soybean seed coats. No difference was observed in either colonic iNOS mRNA or plasma nitric oxide level. These results indicate that anthocyanidins are possible anti-inflammatory agents; however, further studies are required to determine required intake levels in vivo to exert antitumor effect.     

Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines

Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC, and tandem LC-ES/MS, the total cranberry extract (TCE) has been analyzed, quantified, and separated into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins, and anthocyanins (39.4, 30.0, 10.6, 5.5, and 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 microg/mL) versus all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620), and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greater against HCT116 (92.1%) than against HT-29 (61.1%), SW480 (60%), and SW620 (63%). TCE and all fractions showed >/=50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 microg/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins, and flavonol glycosides within the cranberry extract.     

In vitro antioxidant activity and antigenotoxicity of 5-n-alkylresorcinols

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.     

Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison

The effects of resveratrol and pterostilbene (two structurally related stilbene compounds) on three human colon cancer cells were systematically compared. Cell viability tests indicated that IC(50) values of pterostilbene were 2-5-fold lower than those of resveratrol in all three cancer cells. Pterostilbene was also more potent in inhibiting colony formation of all three cancer cells. Annexin V/propidium iodide costaining assay and Western blotting analysis showed pterostilbene had a stronger apoptosis-inducing effect, which was evidenced by the higher percentage of annexin V positive cells and higher levels of cleaved caspase-3 and poly(ADP-ribose) polymerase proteins in cancer cells treated with pterostilbene compared with resveratrol. High-performance liquid chromatography analysis demonstrated that intracellular levels of pterostilbene were 2-4-fold higher than those of resveratrol after treatments with individual compounds at the same concentration. Overall, the results demonstrated that pterostilbene had more potent inhibitory effects on colon cancer cells than resveratrol, which may be associated with the superior bioavailability of pterostilbene to resveratrol.     

Curcuminoids-cellular uptake by human primary colon cancer cells as quantitated by a sensitive HPLC assay and its relation with the inhibition of proliferation and apoptosis

Curcumin, which is a bright orange-yellow pigment of turmeric with antioxidant properties, has been shown to produce a potent preventative action against several types of cancers in recent studies. It has also been reported to protect the development of colon tumor in animals being fed with carcinogen. In the colon cancer cells, curcumin was illustrated to inhibit cell proliferation and induce apoptosis. As an antioxidant, it acts as an anti-inflammatory as well as an antitumor agent. Curcumin has been detected to exist in nature in the form of curcuminoids, a mixture of curcumin, the major component, with two of its related demethoxy compounds (demethoxycurcumin and bisdemethoxycurcumin). In the present study, we have investigated the antiproliferation and induced apoptosis effects of curcuminoids on colon cancer, using the primary cancer cells isolated from Taiwanese colon cancer patients as the model for colorectal cancer. Results showed that curcuminoids inhibited cell proliferation and induced apoptosis of these human primary colon cancer cells. The effects were observed in a dose-dependent manner as dose increased from 12.5 to 100 microM. With the aim of furthering the fundamental understanding of the mechanisms underlying the antiproliferation and induced apoptosis effects of curcuminoids on these human colon cancer cells, we developed a sensitive, rapid, and reproducible assay method based on high-performance liquid chromatography (HPLC). This HPLC technique developed was found to successfully determine, in a quantitative manner, the cellular uptake of curcuminoids. The uptake of these curcuminoids by the colon cancer cells was shown to increase as the dose of curcuminoids was increased. The observations of inhibited proliferation and increased apoptosis in the colon cancer cells appeared to be associated with the cellular uptake of curcuminoids.     

鱿鱼墨黑色素提取物对肿瘤细胞的抑制作用

为探索鱿鱼墨黑色素提取物(SIME)对体外培养的肿瘤细胞的抑制效应,通过四甲基偶氮唑盐(MTT)法和划痕试验比较SIME对人结肠癌细胞HCT-116、宫颈癌细胞Hela、肝癌细胞Hep G2、乳腺癌细胞MCF-7和前列腺癌细胞PC-3增殖及细胞迁移能力的影响。结果表明,SIME对肿瘤细胞形态有不同程度的影响,对肿瘤细胞增殖有浓度依赖性抑制作用,并具有抑制肿瘤细胞非定向迁移的作用。SIME对HCT-116和PC-3细胞增殖的抑制作用较好,72 h时两者半数抑制浓度IC50分别为0.144mg·m L~(-1)和0.485 mg·m L~(-1)。由此可见,SIME具有较强的抗肿瘤活性,该研究结果为鱿鱼墨高值化利用提供了一定的理论依据。     

Perturbation of the EphA2-EphrinA1 System in Human Prostate Cancer Cells by Colonic (Poly)phenol Catabolites

The Eph tyrosine kinase receptors and their ephrin ligands play a central role in human cancer as their deregulated expression induces tumorigenesis with aggressive phenotypes. To evaluate their potential contribution to EphA2-ephrinA1 modulation, several colonic catabolites of dietary (poly)phenolics, known to be generated in vivo, were screened using an ELISA-based binding assay. Some of the catabolites inhibited the binding in a dose-dependent manner (IC(50) values from 0.26 to 43 μM). Functional studies on prostate adenocarcinoma cells revealed that pyrogallol and protocatechuic acid specifically antagonized ephrinA1-Fc-induced EphA2 phosphorylation at concentrations that were not cytotoxic. The active concentrations of pyrogallol appear to be close to what can be reached in vivo under physiological conditions. Finally, because of the roles played by the Eph-ephrin system not only in cancer development but also in neurodegeneration and diabetes, pyrogallol and protocatechuic acid are candidates for more detailed functional studies to elucidate their role in these pathophysiological processes.     

Inhibition of azoxymethane-induced preneoplastic lesions in the rat colon by a cooked stearic acid complexed high-amylose cornstarch

This study evaluated a novel stearic acid complexed high-amylose cornstarch (SAC) for the prevention of preneoplastic lesions in the colon of azoxymethane (AOM)-treated Fisher 344 rats fed resistant starches at 50-55% of the diet for 8 weeks. Uncooked SAC (r-SAC) diet was compared with raw normal-cornstarch diet (r-CS) or raw high-amylose cornstarch diet (r-HA), and water-boiled CS (w-CS) was compared with w-HA and w-SAC, respectively. w-SAC markedly reduced mucin-depleted foci (MDF) numbers compared with w-HA or w-CS. r-HA significantly decreased aberrant crypt foci (ACF) numbers compared with r-CS or r-SAC. Increased cecum weight and decreased cecum pH were observed in the SAC or HA groups. The highest amounts of total or individual short-chain fatty acids (SCFAs) in cecum and of butyrate or propionate in feces were observed in the AOM-treated w-SAC group. This study revealed the effectiveness of a novel resistant starch in inhibiting colonic preneoplastic lesions and the importance of high-moisture cooking on the suppression of colon carcinogenesis by this resistant starch.     

Wheat bran oil and its fractions inhibit human colon cancer cell growth and intestinal tumorigenesis in Apc(min/+) mice

This study was designed to investigate the cancer preventive activities of wheat bran (WB) oil. We studied the colon cancer preventive effects of WB oil and its subfractions in the Apc(min/+) mouse model, a recognized mouse model for human colorectal cancer, and used human colon cancer cell lines (HCT-116 and HT-29) to identify possible active fractions in WB oil. Our results showed that the oil fraction of WB was more active than the water fraction against the growth of human colon cancer cell lines and that 2% WB oil significantly inhibited the overall tumorigenesis by 35.7% (p < 0.0001) in the Apc(min/+) mouse model. The WB oil was further fractioned into nonpolar lipids and phytochemicals and the phytochemical fraction was fractionated into phytosterols and phytosterol ferulates, 5-alk(en)ylresorcinols, and unidentified constituents by normal phase silica gel column chromatography. Results on cell culture showed that the phytochemical fraction had a higher inhibitory effect on HCT-116 human colon cancer cells than that of WB oil, whereas the nonpolar lipid fraction had less growth inhibitory effectiveness. However, neither fractions showed a stronger inhibition than WB oil in the Apc(min/+) mouse model. The current results demonstrate, for the first time, the intestinal cancer preventive activity of WB oil. The active ingredients, however, remain to be identified.     

Synthesis and Inhibitory Activities against Colon Cancer Cell Growth and Proteasome of Alkylresorcinols

We have identified alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer cell growth (HCT-116 and HT-29) using a bioassay-guided approach. To further study the structure-activity relationships, 15 ARs and their intermediates (1-15) were synthesized expediently by the modified Wittig reaction in aqueous media, and six 5-alkylpyrogallols and their analogues (16-21) were prepared by the general Grignard reaction. The synthetic AR analogues were evaluated for activities against the growth of human colon cancer cells HCT-116 and HT-29 and the chymotrypsin-like activity of the human 20S proteasome. Our results found that (1) AR C13:0 and C15:0 (13 and 14) had the greatest inhibitory effects in human colon cancer cells HCT-116 and HT-29, while decreasing or increasing the side chain lengths diminished the activities; (2) two free meta-hydroxyl groups at C-1 and C-3 on the aromatic ring of the AR analogues greatly contributed to their antitumor activity; (3) the introduction of a third hydroxyl group at C-2 (20 and 21) into the aromatic ring of the AR analogues yielded no significant enhancement in activity against HCT-116 cells and decimated the effects against HT-29 cells, but dramatically increased the activity against the chymotrypsin-like activity of the human 20S proteasome; and (4) AR C11:0 (12) was found to have the greatest effect in a series of AR C9:0-C17:0 against the chymotrypsin-like activity of the human 20S proteasome.     

Goniothalamin inhibits growth of human lung cancer cells through DNA damage, apoptosis, and reduced migration ability

We evaluated the possible anticancer performance of a natural compound, goniothalamin (GTN), against human lung cancer using as a non-small cell lung cancer (NSCLC) cell line, H1299, as the model system. Cellular proliferation was significantly inhibited by GTN. Using an improved alkaline comet-nuclear extract (comet-NE) assay, GTN was found to induce a significant increase in the tail DNA. Wound healing and zymography assays showed that GTN attenuated cell migration and caused a reduction in the activity level of two major migration-associated matrix metalloproteinases, MMP-2 and MMP-9. It can be concluded that the DNA-damaging effect of GTN against lung cancer cells leads to growth inhibition as well as a depression in migration ability. Therefore, GTN has potential as a chemotherapeutic agent against lung cancer.