scholarly journals Glutathione conjugation of chlorambucil: measurement and modulation by plant polyphenols

1997 ◽  
Vol 325 (2) ◽  
pp. 417-422 ◽  
Author(s):  
Kai ZHANG ◽  
Kim Ping WONG
Keyword(s):  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Thymidine Uptake ◽  
Dependent Manner ◽  
Glutathione S Transferase ◽  
Plant Polyphenols ◽  
Simultaneous Exposure ◽  
Adenocarcinoma Cells ◽  
Combined Action ◽  
Dose Dependent

Chlorambucil (CMB), an anticancer drug, was cytotoxic at concentrations of 5–20 μM to human colon adenocarcinoma cells. It inhibited [14C]thymidine uptake in a dose-dependent manner. Both effects were potentiated by simultaneous exposure of the cells to 10 μM plant polyphenols. In an attempt to explain the possible mechanism of action of the polyphenols in relation to these observations, an HPLC-radiometric method was developed to measure the conjugation of CMB with glutathione in these cells and to monitor the export of monochloromonoglutathionyl CMB (MG-CMB), its main glutathione conjugate. At micromolar concentrations, five polyphenols, namely quercetin, butein, tannic acid, 2′-hydroxychalcone and morin, inhibited the efflux of CMB significantly; an inhibition of 40% was observed with 10 μM quercetin. The glutathione S-transferase (GST) activity of the cancer cells, measured with 1-chloro-2,4-dinitrobenzene, was also inhibited by the polyphenols. Their combined action on GST and on the efflux of MG-CMB conjugate could provide an enhanced positive modulation of sensitivity of the tumour cells to CMB.

scholarly journals Genoprotective Properties and Metabolites of β-Glucan-Rich Edible Mushrooms Following Their In Vitro Fermentation by Human Faecal Microbiota

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3554
Author(s):  
Athina Boulaka ◽  
Paraschos Christodoulou ◽  
Marigoula Vlassopoulou ◽  
Georgios Koutrotsios ◽  
Georgios Bekiaris ◽  
...  
Keyword(s):  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Edible Mushrooms ◽  
Dependent Manner ◽  
Fungal Cell ◽  
Tert Butyl Hydroperoxide ◽  
Adenocarcinoma Cells ◽  
Health Promoting ◽  
Dose Dependent

A variety of bioactive compounds, constituents of edible mushrooms, in particular β-glucans, i.e., a group of β-d-glucose polysaccharides abundant in the fungal cell walls, have been linked to immunomodulating, anticancer and prebiotic activities. The aim of the study was the investigation of the genoprotective effects of edible mushrooms produced by Pleurotus eryngii, Pleurotus ostreatus and Cyclocybe cylindracea (Basidiomycota). Mushrooms from selected strains of the species mentioned above were fermented in vitro using faecal inocula from healthy volunteers. The cytotoxic and anti-genotoxic properties of the fermentation supernatants (FSs) were investigated in Caco-2 human colon adenocarcinoma cells. The FSs were cytotoxic in a dose-dependent manner. Non-cytotoxic concentrations were used for the genotoxicity studies, which revealed that mushrooms’ FSs have the ability to protect Caco-2 cells against tert-butyl hydroperoxide (t-BOOH), a known genotoxic agent. Their global metabolic profiling was assessed by 1H-NMR spectroscopy. A total of 37 metabolites were identified with the use of two-dimensional (2D) homo- and hetero-nuclear NMR experiments. Multivariate data analysis monitored the metabolic variability of gut microbiota and probed to biomarkers potentially associated with the health-promoting effects of edible mushrooms.

scholarly journals Kinetic analysis of butyrate transport in human colon adenocarcinoma cells reveals two different carrier-mediated mechanisms

2007 ◽  
Vol 409 (1) ◽  
pp. 311-320 ◽  
Author(s):  
Emilio Lecona ◽  
Nieves Olmo ◽  
Javier Turnay ◽  
Angélica Santiago-Gómez ◽  
Isabel López de Silanes ◽  
...  
Keyword(s):  
Anion Exchanger ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Dependent Manner ◽  
High Affinity ◽  
Adenocarcinoma Cells ◽  
Butyrate Treatment ◽  
Human Colon Adenocarcinoma ◽  
Colon Adenocarcinoma Cells ◽  
Resistant Cells

Butyrate has antitumorigenic effects on colon cancer cells, inhibits cell growth and promotes differentiation and apoptosis. These effects depend on its intracellular concentration, which is regulated by its transport. We have analysed butyrate uptake kinetics in human colon adenocarcinoma cells sensitive to the apoptotic effects of butyrate (BCS-TC2, Caco-2 and HT-29), in butyrate-resistant cells (BCS-TC2.BR2) and in normal colonic cells (FHC). The properties of transport were analysed with structural analogues, specific inhibitors and different bicarbonate and sodium concentrations. Two carrier-mediated mechanisms were detected: a low-affinity/high-capacity (Km=109±16 mM in BCS-TC2 cells) anion exchanger and a high-affinity/low-capacity (Km=17.9±4.0 μM in BCS-TC2 cells) proton–monocarboxylate co-transporter that was energy-dependent and activated via PKCδ (protein kinase Cδ). All adenocarcinoma cells analysed express MCT (monocarboxylate transporter) 1, MCT4, ancillary protein CD147 and AE2 (anion exchanger 2). Silencing experiments show that MCT1, whose expression increases with butyrate treatment in butyrate-sensitive cells, plays a key role in high-affinity transport. Low-affinity uptake was mediated by a butyrate/bicarbonate antiporter along with a possible contribution of AE2 and MCT4. Butyrate treatment increased uptake in a time- and dose-dependent manner in butyrate-sensitive but not in butyrate-resistant cells. The two butyrate-uptake activities in human colon adenocarcinoma cells enable butyrate transport at different physiological conditions to maintain cell functionality. The high-affinity/low-capacity transport functions under low butyrate concentrations and may be relevant for the survival of carcinoma cells in tumour regions with low glucose and butyrate availability as well as for the normal physiology of colonocytes.

scholarly journals Antiproliferative Activity on Human Colon Adenocarcinoma Cells and In Vitro Antioxidant Effect of Anthocyanin-Rich Extracts from Peels of Species of the Myrtaceae Family

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 564
Author(s):  
Nayara Simas Frauches ◽  
Júlia Montenegro ◽  
Thuane Amaral ◽  
Joel Pimentel Abreu ◽  
Gabriela Laiber ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Phenolic Compounds ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Native Plant ◽  
Total Anthocyanin ◽  
Adenocarcinoma Cells ◽  
Human Colon Adenocarcinoma ◽  
Colon Adenocarcinoma Cells

There is a significant indication of the beneficial health effects of fruit rich diets. Fruits of native plant species have noticeably different phytochemicals and bioactive effects. The aim of this work was to characterize and compare the constituents of jabuticaba (Myrciaria jaboticaba, MJ), jamun-berry (Syzygium cumini, SC), and malay-apple (Syzygium malaccense, SM) extracts and their influence on antioxidant activity in vitro and antiproliferative effects on human colon adenocarcinoma cells. According to the results, dried peel powders (DP) have a high anthocyanin content, phenolic compounds, and antioxidant activity when compared to freeze dried extracts (FD). M. jaboticaba dried peel powder extract had a higher total anthocyanin and phenolic compounds content (802.90 ± 1.93 and 2152.92 ± 43.95 mg/100 g, respectively). A reduction in cell viability of HT-29 cells after treatment with M. jaboticaba extracts (DP-MJ and FD-MJ) was observed via MTT assay. Flow cytometry showed that the treatment with the anthocyanin-rich extracts from MJ, SC, and SM had an inhibitory impact on cell development due to G2/M arrest and caused a rise in apoptotic cells in relation to the control group. The findings of this study highlight the potential of peel powders from Myrtaceae fruits as an important source of natural antioxidants and a protective effect against colon adenocarcinoma.

scholarly journals Effect of β-carotene-rich tomato lycopene β-cyclase (tlcy-b) on cell growth inhibition in HT-29 colon adenocarcinoma cells

2008 ◽  
Vol 102 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Paola Palozza ◽  
Diana Bellovino ◽  
Rossella Simone ◽  
Alma Boninsegna ◽  
Francesco Cellini ◽  
...  
Keyword(s):  
Cell Growth ◽  
Growth Inhibition ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cell Growth Inhibition ◽  
Adenocarcinoma Cells ◽  
Ht 29 ◽  
Colon Adenocarcinoma Cells ◽  
Β Carotene

Lycopene β-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of β-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced β-carotene release and therefore cell growth inhibition. To induce with purified β-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that β-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with β-carotene in promoting cell growth arrest.

scholarly journals Inhibition of Fungal Appressorium Formation by Pepper (Capsicum annuum) Esterase

2001 ◽  
Vol 14 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Young Soon Kim ◽  
Hyun Hwa Lee ◽  
Moon Kyung Ko ◽  
Chae Eun Song ◽  
Cheol-Yong Bae ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Capsicum Annuum ◽  
Magnaporthe Grisea ◽  
Dependent Manner ◽  
Appressorium Formation ◽  
Glutathione S Transferase ◽  
Porcine Liver ◽  
Esterase Gene ◽  
Dose Dependent ◽  
Dependent Signaling Pathway

A pepper esterase gene (PepEST) that is highly expressed during an incompatible interaction between pepper (Capsicum annuum) and the anthracnose fungus Colletotrichum gloeosporioides has been previously cloned. Glutathione-S-transferase-tagged recombinant PepEST protein expressed in Escherichia coli showed substrate specificity for p-nitrophenyl esters. Inoculation of compatible unripe pepper fruits with C. gloeosporioides spores amended with the recombinant protein did not cause anthracnose symptoms on the fruit. The recombinant protein has no fungicidal activity, but it significantly inhibits appressorium formation of the anthracnose fungus in a dose-dependent manner. An esterase from porcine liver also inhibited appressorium formation, and the recombinant protein inhibited appressorium formation in the rice blast fungus, Magnaporthe grisea. Inhibition of appressorium formation in M. grisea by the recombinant protein was reversible by treatment with cyclic AMP (cAMP) or 1,16-hexadecanediol. The results suggest that the recombinant protein regulates appressorium formation by modulating the cAMP-dependent signaling pathway in this fungus. Taken together, the PepEST esterase activity can inhibit appressorium formation of C. gloeosporioides, which may result in protection of the unripe fruit against the fungus.

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