Mushrooms have become popular sources of natural antitumor, antiviral, antibacterial, antioxidative, and immunomodulatory agents. Golden oyster mushroom, Pleurotus citrinopileatus , is a common mushroom in oriental countries for human consumption. We isolated a functional protein (PCP-3A) from the fresh fruiting body of this mushroom. The isolation procedure included ammonium sulfate fractionation, DEAE-Sepharose CL-6B ion exchange chromatography, and Sephacryl S-300 gel filtration. Electrophoresis demonstrated that PCP-3A is a glycoprotein composed of 10 subunits, each approximately 45.0 kDa in size. In vitro cell study showed that PCP-3A at a concentration about 12.5 microg/mL inhibits the proliferation of human tumor cell line U937, in a time- dependent manner (24, 48, and 72 h). It failed to agglutinate rabbit and human erythrocytes, excluding its possibility from being a lectin. Flow cytometry revealed that it is capable of inhibiting the growth of U937 cells by way of S phase arrest and apoptotic induction. We suggest that PCP-3A is worth further investigating for antitumor use.

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem‑like cells (GSCs), by culturing patient‑derived primary GSCs as well as a GSC cell line in glucose‑restricted, β‑hydroxybutyrate‑containing medium (BHB‑Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB‑Glow medium exhibited reduced proliferation and increasedapoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self‑renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB‑Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB‑Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia‑inducible factor 1 and B‑cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB‑Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.

The objective of the present study was to isolate a lectin from fresh fruiting bodies of the mushroom Pleurotus citrinopileatus and examine it for various biological activities. The isolation procedure comprised ion exchange chromatography on DEAE-cellulose, CM-celluloses, and Q-Sepharose, and gel filtration on Superdex 75. A homodimeric 32.4 kDa lectin displaying high hemagglutinating activity was isolated with over 110 fold of purification. Its N-terminal amino acid sequence, QYSQMAQVME, has not been reported for other lectins. The lectin was unadsorbed on DEAE-cellulose in 0.001 M NH4HCO3 buffer (pH 9.4), but adsorbed on CM-cellulose in 0.001 M NH4OAc buffer (pH 4.8) and eluted by approximately 0.05 M NaCl in the same buffer. The lectin was subsequently adsorbed on Q-Sepharose and eluted by a linear gradient of 0-0.2 M NaCl in 10 mM NH4HCO3 buffer (pH 8.5). The lectin was obtained in a purified form after gel filtration by fast protein liquid chromatography on Superdex 75. The hemagglutinating activity of the lectin was inhibited by maltose, O-nitrophenyl-beta-d-galactopyranoside, O/P-nitrophenyl-beta-d-glucuronide and insulin. It was stable at temperatures up to 60 degrees C, and in NaOH and HCl solutions up to 0.1 M and 0.006 M concentration, respectively. It was sensitive to inhibition by HgCl2 and potentiation by AlCl3. The lectin exerted potent antitumor activity in mice bearing sarcoma 180, and caused approximately 80% inhibition of tumor growth when administered intraperitonealy at 5 mg/kg daily for 20 days. It elicited a mitogenic response from murine splenocytes in vitro with the maximal response at a lectin concentration of 2 microM. The lectin inhibited HIV-1 reverse transcriptase with an IC50 of 0.93 microM. It was devoid of antifungal activity.

Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumors by administration of glucose (+/- insulin) and by drugs such as hydralazine which modify the relative blood flow to tumors and normal tissues. Cells have evolved mechanisms for regulating their intracellular pH. The amiloride-sensitive Na+/H+ antiport and the DIDS-sensitive Na+-dependent HCO3-/Cl- exchanger appear to be the major mechanisms for regulating pHi under conditions of acid loading, although additional mechanisms may contribute to acid extrusion. Mitogen-induced initiation of proliferation in some cells is preceded by cytoplasmic alkalinization, usually triggered by stimulation of Na+/H+ exchange; proliferation of other cells can be induced without prior alkalinization. Mutant cells which lack Na+/H+ exchange activity have reduced or absent ability to generate solid tumors; a plausible explanation is the failure of such mutant cells to withstand acidic conditions that are generated during tumor growth. Studies in tissue culture have demonstrated that the combination of hypoxia and acid pHe is toxic to mammalian cells, whereas short exposures to either factor alone are not very toxic. This interaction may contribute to cell death and necrosis in solid tumors. Acidic pH may influence the outcome of tumor therapy. There are rather small effects of pHe on the response of cells to ionizing radiation but acute exposure to acid pHe causes a marked increase in response to hyperthermia; this effect is decreased in cells that are adapted to low pHe. Acidity may have varying effects on the response of cells to conventional anticancer drugs. Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi. It is suggested that acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.

The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead acetate in diet as 500 mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1 mg/100g body weight) and silymarin (1 mg/100g body weight) by gastric tube three times per week. Blood samples were taken after 2, 4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver tissue.

Anti-proliferative and pro-apoptotic activities of fractions of Pleurotus ostreatus were examined using HT-29 colon cancer cells in vitro. A hot-water-soluble fraction of the mycelium of the liquid cultured mushroom was partially isolated and chemically characterized as a low-molecular-weight alpha-glucan. HT-29 cells were exposed to the different isolates and significant inhibition of proliferation was obtained in a dose-dependent manner. Proliferation inhibition was shown to be the result of apoptotic induction because the pro-apoptotic molecules Bax and cytosolic cytochrome-c were upregulated. Fluorescence-activated cell sorter analyses of polysaccharide-treated HT-29 cells showed a high percentage of Annexin-positive cells. Here, we describe a newly identified low-molecular-weight alpha-glucan with promising anti-tumorigenic properties, and demonstrate its direct effect on colon cancer cell proliferation via induction of programmed cell death.

Mushroom Inonotus obliquus (I. obliquus) has been used as functional food and traditional Chinese herbs for long time. An efficient method for bioassay-guided preparative isolation was used for identifying the anti-inflammatory and anticancer constituents in I. obliquus. The petroleum ether and ethyl acetate fractions were found to have significant inhibition effects on NO production and NF-κB luciferase activity in macrophage RAW 264.7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231. Six main constituents were isolated from these two fractions and they were identified as lanosterol (1), 3β-hydroxy-8,24-dien-21-al (2), ergosterol(3), inotodiol (4), ergosterol peroxide (5) and trametenolic acid (6). Compound ergosterol, ergosterol peroxide and trametenolic acid showed anti-inflammatory activities and ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA-MB-231 cell. The results obtained in this work might contribute to understanding the biological activity of mushroom I. obliquus for food and drug application.

BACKGROUND:Ginger (Zingiber officinale Rosc.) belongs to the family Zingiberaceae. The health-promoting perspective of ginger is attributed to its rich phytochemistry. This study aimed to review the current evidence on ginger effects as an anti-inflammatory and anti-oxidative.

METHODS:We searched MEDLINE for related publications using"ginger"and"anti-oxidative"and"ginger"and"anti-inflammatory"as keywords. This search had considered Papers that had been published between 2000 and 2010 without any filter.

CONCLUSIONS:The anticancer potential of ginger is well documented and its functional ingredients like gingerols, shogaol, and paradols are the valuable ingredients which can prevent various cancers. This review concludes to favor ginger but some ambiguities necessitate further research before claiming its efficacy.

, within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted fromhave revealed anticancer, antioxidant and liver protective effects.has been associated with prostate cancer cells.extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from(GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

The medicinal mushroom Chaga, Inonotus obliquus (Pers.:Fr.) Pilát (Hymenochaetaceae), has been used in folk medicine in Russia, Poland, and most of the Baltic countries, as a cleansing and disinfecting measure, and as decoctions for stomach diseases, intestinal worms, liver and heart ailments, and cancer treatment. Many reports have been published concerning the health promoting functions of this mushroom, including antibacterial, hepatoprotective, anti-inflammatory, antitumor, and antioxidant activities. The purpose of the present study was evaluation of in vitro anticancer activity of fraction IO4 isolated from I. obliquus. The effect on cell proliferation, motility and viability was assessed in a range of cancer and normal cells. Chaga fraction prepared from dried fruiting bodies was subjected to anticancer evaluation in human lung carcinoma (A549), colon adenocarcinoma (HT-29), and rat glioma (C6) cell cultures. Human skin fibroblasts (HSF), bovine aorta endothelial cells (BAEC), models of rat oligodendrocytes (OLN-93), hepatocytes (Fao), rat astroglia, and mouse neurons (P19) were applied to test toxicity in normal cells. The following methods were applied: tumor cell proliferation (MTT assay and BrdU assay), cytotoxicity (LDH assay), tumor cell motility (wound assay), tumor cell morphology (May-Grünwald-Giemsa staining), and death detection (ELISA). Chaga fraction elicited anticancer effects which were attributed to decreased tumor cell proliferation, motility and morphological changes induction. Of note is the fact that it produced no or low toxicity in tested normal cells. The data presented could open interesting paths for further investigations of fraction IO4 as a potential anticancer agent.

Non-Hodgkin lymphomas incidence has increased more than 70% in last 25 years. Aggressiveness, higher relapse rate, and treatment complications pose significant barriers. Decreased food intake and side effects of treatments make cancer patients vulnerable to deficiency of essential nutrients such as vitamin C, lysine, and proline leading to the formation of weak extra cellular matrix susceptible to easy breakdown by matrix metalloproteinase enzymes. Inhibition of these enzymes has shown promise in stopping metastasis. Aim: In this study, we investigated the effects of a specific nutrient mixture, containing ascorbic acid, lysine, proline, green tea extract among others, in most aggressive forms of non-Hodgkin's lymphoma - Burkitt's lymphoma, and T-cell lymphoma - using Raji and Jurkat cells respectively. Methods: Nutrient mixture (NM) doses of 0, 10, 50, 100, 500, 1000 microg/ml, were used to study effects on cell proliferation, expression of matrix metalloproteinase, Matrigel invasion and apoptosis. Results: The results demonstrated that the dose response toxicity of the nutrient mixture on Raji cells gradually increased with increasing concentration. The nutrient mixture was non-toxic to Jurkat cells, however exhibited anti-proliferative properties at higher concentrations. Zymography demonstrated, NM had a significant inhibitory effect on matrix metalloproteinase-9 expression with total inhibition at 1000 microg/ml for Raji cells and at 500 microg/ml for Jurkat cells. The NM at 100 microg/ml completely inhibited Matrigel invasion for Raji cells, and at 1000 microg/ml for Jurkat cells. After the NM challenge virtually all Raji and Jurkat cells exposed to 1000 microg/ml were in late apoptosis. Conclusion: Considering the lack of treatment options and continually increasing incidence, NM could be further explored for its therapeutic potential in Burkitt's lymphoma and T-cell lymphoma.

Background:is a medicinal plant called rosemary, largely used in the Mediterranean diet for many decades ago.

Objective:The aim of the present study was to investigate the polyphenolic content, the antioxidant activity, and the antiproliferative effect against human prostate cancer cell lines (LNCaP) of carnosol and carnosic acid as bioactive compounds contained ingrowing in Morocco.

Materials and Methods:Polyphenolic content ofethanolic extract was studied using colorimetric assay. Carnosol and carnosic acid contained inextract were quantified using high-performance liquid chromatography (HPLC). The antiproliferative effect of the studied extracts on LNCaP was evaluated by WST-1 bioassay, and the antioxidant activity was assessed using DPPH assay.

Results:The extracts ofshowed an important polyphenolic content ranging from 74.15 g·GAE/mg to 146.63 g·GAE/mg. The percentage of carnosol and carnosic acid in rosemary crops ranges from 11.7 to 17.3% and 1.09% to 3%, respectively. The extracts ofexhibited a promoting antioxidant activity with ICranging from 0.236 mg/mL to 0.176 mg/mL. Regarding the antiproliferative effect, the WST-1 assay revealed that all the tested extracts reduced notably the cell viability with ICvalues ranging from 14.15 to 15. 04 g/mL.

Conclusion:In the current work, carnosol and carnosic acid exhibit antioxidant and antiproliferative activities in a concentration-dependent manner.

We analyzed the antiproliferative activity of 6 medicinal wood-destroying mushrooms (Fomes fomentarius, Fomitopsis pinicola, Trametes versicolor, Trichaptum biforme, Inonotus obliquus, and Coniophora puteana) that are common in deciduous and mixed coniferous forests in Central Russia. Morphological identification of strains collected from the wild was confirmed based on ribosomal DNA internal transcribed spacer phylogenetic analysis. We observed cytotoxic and cell growth-inhibitory effects of hot water extracts from mycelial biomass of 5 species-T. versicolor, C. puteana, F. fomentarius, F. pinicola, and I. obliquus-on leukemia cell lines (Jukart, K562, and THP-1); the effective extract concentrations were mostly less than 50μg · mL-1. However, we observed no antiproliferative activity of dry biomass from methanol-chloroform (1:1) extracts of C. puteana and F. fomentarius. A chemosensitivity assay showed that the most effective polypore mushroom extract was the methanol extract of T. versicolor (strain It-1), which inhibited the growth of 6 various solid tumors (A-549 and SWi573 [lung], HBL-100 and T-47D [breast], HeLa [cervix], and WiDr [colon]) at concentrations below 45 μg · mL-1, with a concentration as low as 0.7-3.6 μg · mL-1 causing 50% reduction in the proliferation of cancer cells in lung and cervixtumors. Methanol extracts of F. pinicola and I. obliquus were less effective, with proliferation-inhibiting capacities at concentrations below 70 and 200 μg · mL-1, respectively. Thus, T. versicolor is a prospective candidate in the search for and production of new antiproliferative chemical compounds.

is a non-photosynthetic plant that grows in Mediterranean countries and that is amply used in the traditional medicine. The aim of this study was to extend previous studies on the chemical and biological properties ofevaluating the potential antiviral and antiproliferative activity of the methanolic extract. The MTT assay was used for thecytotoxic studies against human cancer-derived cell lines, while both MTT and plaque reduction (PRT) methods were used to evaluate the potential inhibitory effect of the extract against a panel of mammal viruses. The results obtained showed no selective activity against any DNA and RNA virus but revealed an interesting antiproliferative activity against human leukaemia-derived cell lines.

Chamomile (Matricaria chamomilla), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7-O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.

We investigated the suppressive effects of crocin alone and in combination with hyperthermia (HT) on proliferation of breast cancer cells. Cell viability, colony formation ability, and apoptosis were assessed by 3-(4,5-dimetylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), soft agar, Hoechst 33258 staining, and percentage of lactate dehydrogenase (LDH) release methods, respectively. The mRNA levels Hsp27, Hsp70, Hsp90, Bax, and Bcl-2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hsp70 and Hsp90 proteins were determined using enzyme-linked immunosorbent assay (ELISA) technique. Crocin in combination with HT significantly inhibited the proliferation of cancer cells in a dose- and time-dependent manner. There was a degree of synergism in the combined treatment. However, crocin did not show the high cytotoxic effect on normal cells. This treatment decreased colony formation of cancer cells up to 94%. Changed nuclear morphology and increased LDH indicated that crocin combined with HT has a more apoptotic effect than crocin alone. Furthermore, in treated cells Bax/Bcl-2 ratio markedly increased, whereas expression of heat-induced genes decreased. Also, the Hsp70 and Hsp90 proteins decreased in the treated cells. Our study indicated that combination of crocin and HT has strong antiproliferative and apoptotic activities against breast cancer cells. Hence, it is suggested that more studies are warranted to apply crocin as a possible, safe, and promising anticancer agent in cancer.

We investigated the suppressive effects of crocin alone and in combination with hyperthermia (HT) on proliferation of breast cancer cells. Cell viability, colony formation ability, and apoptosis were assessed by 3-(4,5-dimetylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), soft agar, Hoechst 33258 staining, and percentage of lactate dehydrogenase (LDH) release methods, respectively. The mRNA levels Hsp27, Hsp70, Hsp90, Bax, and Bcl-2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hsp70 and Hsp90 proteins were determined using enzyme-linked immunosorbent assay (ELISA) technique. Crocin in combination with HT significantly inhibited the proliferation of cancer cells in a dose- and time-dependent manner. There was a degree of synergism in the combined treatment. However, crocin did not show the high cytotoxic effect on normal cells. This treatment decreased colony formation of cancer cells up to 94%. Changed nuclear morphology and increased LDH indicated that crocin combined with HT has a more apoptotic effect than crocin alone. Furthermore, in treated cells Bax/Bcl-2 ratio markedly increased, whereas expression of heat-induced genes decreased. Also, the Hsp70 and Hsp90 proteins decreased in the treated cells. Our study indicated that combination of crocin and HT has strong antiproliferative and apoptotic activities against breast cancer cells. Hence, it is suggested that more studies are warranted to apply crocin as a possible, safe, and promising anticancer agent in cancer.

BACKGROUND: Ascorbic acid (AA), or Vitamin C, is most well known as a nutritional supplement with antioxidant properties. Recently, we demonstrated that high concentrations of AA act on PMP22 gene expression and partially correct the Charcot-Marie-Tooth disease phenotype in a mouse model. This is due to the capacity of AA, but not other antioxidants, to down-modulate cAMP intracellular concentration by a competitive inhibition of the adenylate cyclase enzymatic activity. Because of the critical role of cAMP in intracellular signalling, we decided to explore the possibility that ascorbic acid could modulate the expression of other genes. METHODS AND FINDINGS: Using human pangenomic microarrays, we found that AA inhibited the expression of two categories of genes necessary for cell cycle progression, tRNA synthetases and translation initiation factor subunits. In in vitro assays, we demonstrated that AA induced the S-phase arrest of proliferative normal and tumor cells. Highest concentrations of AA leaded to necrotic cell death. However, quiescent cells were not susceptible to AA toxicity, suggesting the blockage of protein synthesis was mainly detrimental in metabolically-active cells. Using animal models, we found that high concentrations of AA inhibited tumor progression in nude mice grafted with HT29 cells (derived from human colon carcinoma). Consistently, expression of tRNA synthetases and ieF2 appeared to be specifically decreased in tumors upon AA treatment. CONCLUSIONS: AA has an antiproliferative activity, at elevated concentration that could be obtained using IV injection. This activity has been observed in vitro as well in vivo and likely results from the inhibition of expression of genes involved in protein synthesis. Implications for a clinical use in anticancer therapies will be discussed.

Ganoderma lucidum, a mushroom that has been used to treat disease in East Asia for centuries, has been shown to be effective against many types of tumors, but the exact cellular mechanism of action is unknown. In this study we examined proliferation of a lung cancer cell line after treatment with 12 concentrations of powdered G. lucidum for 24, 48, and 120 hours. Based on half-maximal inhibitory concentrations values, proliferation of the H1793 cell line seemed to be sensitive to the extract in a time- and dose-dependent manner. We used immunoblot analysis to examine the amounts of cell cycle proteins (cyclin D, Cdk4, and Cdc2) and apoptotic proteins (Bcl-xL and Bax) after treatment with a range of G. lucidum concentrations. Changes in amounts of proteins that regulate the cell cycle were consistent with longer G1 and G2 phases. Proapoptotic protein (Bax) levels increased 6.5-fold, with a commensurate increase in the Bax-to-Bcl ratio, especially at 48 and 120 hours. These results suggest that the decrease in cellular proliferation correlated with a change in both cell cycle progression and apoptosis, and that the triterpenoid in G. lucidum is the bioactive component. Further biochemical characterization of this ancient herbal remedy could hold promise for treating lung cancer.