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![Synergy between FWGE and 5-FU in human colon cancer cell line HCT15. Plots represent the average of 3 independent experiments. The hypothetical curve was calculated as described by Drewinko et al. [16]. Synergy is indicated by the hypothetical curve which runs above the combination curve.](profile/Wieland-Voigt/publication/51054287/figure/fig3/AS:202894457479170@1425385216119/Synergy-between-FWGE-and-5-FU-in-human-colon-cancer-cell-line-HCT15-Plots-represent-the.png)
Synergy between FWGE and 5-FU in human colon cancer cell line HCT15. Plots represent the average of 3 independent experiments. The hypothetical curve was calculated as described by Drewinko et al. [16]. Synergy is indicated by the hypothetical curve which runs above the combination curve.
Source publication
Fermented wheat germ extract (FWGE) is currently used as nutrition supplement for cancer patients. Limited recent data suggest antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to...
Context in source publication
Citations
... Fermented wheat germ extract (FWGE), or Avemar, is an over-the-counter nutritional supplement that has been utilized by cancer patients since the discovery of its anticancer properties [4]. There is a wealth of published data demonstrating the ability of FWGE to inhibit cancer cell growth in vitro in malignancies such as ovarian, hepatocellular, T cell leukemia and B cell lymphoma, melanoma, squamous cell oral cancer, breast cancer and colon cancer as a monotherapy or when combined with other agents [5][6][7][8][9][10][11][12]. Control of tumor growth has been demonstrated in animal models of melanoma, colon cancer, and lymphoma [4,10,12,13]. ...
... The IC 50 values for NSCLC cell lines include 71.74 µg/mL (A549), 20.99 ug/mL (Calu-1), and 12.88 µg/mL (H1975). Notably, against A549 cells, we found our protein formulation to be~3 times more potent than FWGE, as measured previously by another group [5]. Although the FWGP IC 50 for A549 was the highest among the cell lines we tested, we chose to focus the remainder of this study on A549 because: (a) it is among the most commonly used lines in NSCLC studies; and (b) we reasoned that in vivo efficacy vs. A549 would suggest that other cell types from Table 1 could potentially respond to FWGP treatment. ...
... Increasingly, patients are seeking alternative or complementary medicine either to treat their disease or prevent it [24]. One nutraceutical, FWGE, has demonstrated potential as a cytotoxic agent against multiple malignant cell lines in vitro such as colorectal carcinoma, melanoma, breast cancer, and lung cancer and has demonstrated in vivo tumor control in colon and melanoma models [4,5,10]. However, rigorous scientific analysis to confirm its efficacy in NSCLC is lacking. ...
Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the need remains for non-toxic, effective NSCLC therapies, especially in an elderly patient population. Our lab has previously identified a protein fraction from the nutraceutical Avemar®—dubbed fermented wheat germ protein (FWGP)—with demonstrated efficacy in lymphoma models both in vitro and in vivo. Here, we show that FWGP also has anti-tumor activity in vitro and in vivo against lung cancer. In vitro cytotoxicity against multiple lung cancer cell lines yielded IC50 values comparable to those previously established with the parent product, Avemar. Further, significant A549 xenograft growth inhibition occurred in athymic nu/nu mice receiving FWGP in both pre-radiated and non-radiated models when compared to the untreated control. Encouragingly, mice treated with FWGP experienced no toxicities as detected by weight reduction or blood chemistry analysis. These data support the further study of FWGP as a potential non-toxic therapy for lung cancer and other oncologic indications.
... It should be stressed that WGO is a vegetable oil with anti-inflammatory and antioxidant properties [37,38]. A previous study [72] reported that fermented wheat germ extract stimulates cell apoptosis and inhibits the proliferation of cancer cells. Regarding its antiparasitic effects, wheat germ extract reported antiparasitic activity against Giardia lamblia in combination with probiotics [73]. ...
... It should be stressed that WGO is a vegetable oil with anti-inflammatory and antioxidant properties [37,38]. A previous study [72] reported that fermented wheat germ extract stimulates cell apoptosis and inhibits the proliferation of cancer cells. Regarding its antiparasitic effects, wheat germ extract reported antiparasitic activity against Giardia lamblia in combination with probiotics [73]. ...
Toxoplasmosis is one of the most common parasitic zoonoses that affects all vertebrates. The drugs most commonly used against toxoplasmosis have many side effects, making the development of new antiparasitic drugs a big challenge. The present study evaluated the therapeutic effectiveness of novel herbal treatments, including propolis and wheat germ oil (WGO), against acute toxoplasmosis. A total of 50 albino mice were divided into five groups: group 1 (G1) (non-infected and non-treated); group 2 (G2) (infected without treatment); group 3 (G3) (treated with propolis); group 4 (G4) (treated with WGO); group 5 (G5) (treated with a combination of propolis and WGO). The effects of the herbal substances on different organs, mainly liver, spleen, and lungs, were investigated using parasitological, molecular, and histopathological examinations. The results of parasitological examination demonstrated statistically significant (p < 0.05) differences in the parasitic load between treated groups (G3, G4, and G5) compared to the control positive group (G2). These differences were represented by a significant reduction in the parasite load in stained tissue smears from the liver obtained from the animals treated with propolis (G3) compared to the parasite load in the positive control group. Similarly, animals (G4) treated with WGO exhibited a significant reduction in the parasite load versus the positive control group, while the lowest parasite load was found in G5, treated with propolis and WGO. Quantification of the parasite burden through molecular methods (PCR) revealed similar findings represented by reduction in the parasite burden in all treated groups with WGO and propolis as compared to the control group. Importantly, these previous parasitological and molecular findings were accompanied by a marked improvement in the histopathological picture of the liver, spleen, and lungs. In conclusion, propolis and WGO showed a good combination of therapeutic efficacy against acute toxoplasmosis.
... Oral squamous cell carcinoma (OSCC) represents one of the most aggressive types of cancers with over 350,000 new cases and 146,000 deaths in 2015 worldwide (1,2). The incidence of OSCC, and especially oral tongue carcinoma (OTSCC), is increasing and the average age of the affected patients is decreasing (3). The etiologic factors for OSCC include tobacco, alcohol, betel quid or a combined consumption of them. ...
... To assess the effects of FWGE on cell viability of OTSCC cell lines, cells were treated with different concentrations of the compound and analyzed by MTT assay was performed at time points 24, 48 and 72 h. The concentrations of FWGE were decided based on the previous studies (3,19,25,26). An initial experiment of cell viability was carried out by testing three concentrations (0.1, 1 and 10 mg/ml). ...
... Several natural compounds have been analyzed to explore their potential anticancer properties for disease prevention (27) or importantly, also to improve the current cancer treatment and reduce the side effects of common anticancer therapies (28,29). The extract of wheat germ fermented by Saccharomyces cerevisiae contains a high amount of benzoquinone that exerts an antiproliferative and cytotoxic activity against several tumor cells (3,16). In this study, the effects of FWGE on highly aggressive and metastatic HSC-3, invasive SAS, as well as on less invasive SCC-25 OTSCC cell lines (30)(31)(32)(33)(34) were investigated to see if FWGE affects their viability, migration and invasion. ...
Oral carcinoma is one of the most aggressive cancers, and despite the advances in the therapy, its mortality is still high. An attention in cancer treatment has focused on natural compounds due to their potential beneficial effects on human health. In this study, the effects of dietary supplement Fermented Wheat Germ Extract (FWGE) on oral tongue squamous cell carcinoma (OTSCC) cells were investigated In Vitro using three cell lines (HSC-3, SAS, SCC-25) with variable aggressiveness. The cell viability was significantly decreased by the treatment with high concentration of FWGE in every cell line. Regarding migration and invasion, HSC-3 and SCC-25 cells were most sensitive to FWGE since their movement was significantly reduced with 5 and 10 mg/ml FWGE, while SAS was inhibited only with 10 mg/ml FWGE. Chemotherapeutic compounds (cisplatin and 5-fluorouracil) significantly reduced all OTSCC cells viability. Importantly, combination of these drugs with 10 mg/ml FWGE significantly decreased the cell viability compared to the treatment with the chemotherapeutics or FWGE alone. Based on these In Vitro experiments, the use of FWGE seems to improve the anticancer effects on OTSCC cells. Further In Vivo and clinical studies should be conducted to verify the positive effects of FWGE for OTSCC patients.
... Fermented wheat germ extract possesses preventive and therapeutic functions in various cancer cells [23,24]. 2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ), a derivative of fermented wheat germ extract, is found in sourdough fermentation of wheat germ and other fermented foods. ...
Background:
Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.
Methods:
Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models.
Results:
2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model.
Conclusions:
2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients.
... Fermentation can increase the release of hydroquinones in wheat germ [5,6]. Several studies have shown that the water extract of wheat germ fermented with yeast exhibits anti-cancer effects [4,[7][8][9], and the extract is commercially available as a nutritional supplement for cancer patients. Hidvegi, who first patented the water extract of fermented wheat germ, established MBQ and DMBQ as quality markers for its manufacture. ...
Wheat germ is rich in quinones that exist as glycosides. In this study, we used Celluclast 1.5L to release the hydroxyquinones, which turn into benzoquinone, and prepared the water extract from enzyme-treated wheat germ (EWG). We investigated whether enzyme treatment altered the anti-inflammatory activity compared to the water extract of untreated wheat germ (UWG). UWG inhibited the production of inducible nitric oxide synthase (iNOS) and interleukin (IL)-12 and induced the production of IL-10 and heme oxygenase (HO)-1 in lipopolysaccharide (LPS)-stimulated macrophages. Enzyme treatment resulted in greater inhibition of iNOS and IL-10 and induction of HO-1 compared to UWG, possibly involving the modulation of nuclear factor (NF)-κB, activator protein 1 (AP-1) and nuclear factor erythroid 2-related factor (Nrf2). Mice fed UWG or EWG had decreased serum tumor necrosis factor (TNF)-α and increased serum IL-10 levels after intraperitoneal injection of LPS, with UWG being more effective for IL-10 and EWG more effective for TNF-α. Hepatic HO-1 gene was only expressed in mice fed EWG. We provide evidence that enzyme treatment is a useful biotechnology tool for extracting active compounds from wheat germ.
... After duplicates were removed, 20 studies were identified as acceptable for full-text evaluation and their full texts were read. At the end of the selection process, 16 articles [13,18,19,[21][22][23][24][25][26][27][28][29][30][31][32][33] were included in qualitative analysis, while four [9,17,35,36] were excluded for not complying with inclusion criteria. ...
... (1) Jurkat leukemic T cells were studied by three studies [18,21,32] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis; (2) Lymphoma cells were subjected to the treatment and the effects investigated by three studies [21,27,32] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects; (3) Gastric cancer cell line experiments reported in three papers [22,25,26] found antiproliferative, cytotoxic, cytostatic, and growth-delay effects; (4) Ovarian cancer cell lines, when subjected to treatment with AVEMAR, showed cytotoxic effects [23], antiproliferative activity [25], and suppression of cell proliferation [29]; ...
... (1) Jurkat leukemic T cells were studied by three studies [18,21,32] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis; (2) Lymphoma cells were subjected to the treatment and the effects investigated by three studies [21,27,32] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects; (3) Gastric cancer cell line experiments reported in three papers [22,25,26] found antiproliferative, cytotoxic, cytostatic, and growth-delay effects; (4) Ovarian cancer cell lines, when subjected to treatment with AVEMAR, showed cytotoxic effects [23], antiproliferative activity [25], and suppression of cell proliferation [29]; ...
... After duplicates were removed, 20 studies were identified as acceptable for full-text evaluation and their full texts were read. At the end of the selection process, 16 articles [13,18,19,[21][22][23][24][25][26][27][28][29][30][31][32][33] were included in qualitative analysis, while four [9,17,35,36] were excluded for not complying with inclusion criteria. ...
... (1) Jurkat leukemic T cells were studied by three studies [18,21,32] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis; (2) Lymphoma cells were subjected to the treatment and the effects investigated by three studies [21,27,32] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects; (3) Gastric cancer cell line experiments reported in three papers [22,25,26] found antiproliferative, cytotoxic, cytostatic, and growth-delay effects; (4) Ovarian cancer cell lines, when subjected to treatment with AVEMAR, showed cytotoxic effects [23], antiproliferative activity [25], and suppression of cell proliferation [29]; ...
... (1) Jurkat leukemic T cells were studied by three studies [18,21,32] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis; (2) Lymphoma cells were subjected to the treatment and the effects investigated by three studies [21,27,32] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects; (3) Gastric cancer cell line experiments reported in three papers [22,25,26] found antiproliferative, cytotoxic, cytostatic, and growth-delay effects; (4) Ovarian cancer cell lines, when subjected to treatment with AVEMAR, showed cytotoxic effects [23], antiproliferative activity [25], and suppression of cell proliferation [29]; ...
Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.
... The extract has been standardized to DMBQ content and named MSC (trade name: AVEMAR) [9-11]. Crude fermented wheat germ extract (FWGE) has been shown to be cytotoxic in various malignant cells lines, including T-cell leukemia [12,13], colorectal carcinoma [14, 15], promyelocytic leukemia [16], hepatocellular carcinoma [17], pancreatic carcinoma [18] and ovarian carcinoma [19,20], as well as neuroblastoma, melanoma and testicular, cervical, thyroid and lung carcinoma-derived cell lines [20]. Anti-tumor and anti-metastatic activity of FWGE in animal models has been reported in melanoma and in squamous cell, lung and colorectal carcinomas [9, 10, 21-23]; preliminary clinical trial data in melanoma [24] and colorectal carcinoma [23,25] are promising. ...
... The extract has been standardized to DMBQ content and named MSC (trade name: AVEMAR) [9-11]. Crude fermented wheat germ extract (FWGE) has been shown to be cytotoxic in various malignant cells lines, including T-cell leukemia [12,13], colorectal carcinoma [14, 15], promyelocytic leukemia [16], hepatocellular carcinoma [17], pancreatic carcinoma [18] and ovarian carcinoma [19,20], as well as neuroblastoma, melanoma and testicular, cervical, thyroid and lung carcinoma-derived cell lines [20]. Anti-tumor and anti-metastatic activity of FWGE in animal models has been reported in melanoma and in squamous cell, lung and colorectal carcinomas [9, 10, 21-23]; preliminary clinical trial data in melanoma [24] and colorectal carcinoma [23,25] are promising. ...
... This result not only confirms in vivo activity of the protein fraction but also indicates increased potency. Previous reports suggested small molecules such as benzoquinones were responsible for FWGE activity [20]. Our process to produce FWGP from FWGE eliminates small molecules and leaves primarily proteins. ...
Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the disease. Many patients explore less toxic alternative therapeutics proposed to boost anti-tumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented wheat germ. Fermented wheat germ extract was produced by fermenting wheat germ with Saccharomyces cerevisiae. A protein fraction was tested for lymphomacidal activity in vitro using NHL cell lines and in vivo using mouse xenografts. Mechanisms of action were explored in vitro by evaluating apoptosis and cell cycle and in vivo by immunophenotyping and measurement of NK cell activity. Potent lymphomacidal activity was observed in a panel of NHL cell lines and mice bearing NHL xenografts. This activity was not dependent on wheat germ agglutinin or benzoquinones. Fermented wheat germ proteins induced apoptosis in NHL cells, and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation and production of IFNγ. Fermented wheat germ extract can be easily produced and is efficacious in a human lymphoma xenograft model. The protein fraction is quantifiable and more potent, shows direct pro-apoptotic properties, and enhances immune-mediated tumor eradication. The results presented herein support the novel concept that proteins in fermented wheat germ have direct pro-apoptotic activity on lymphoma cells and augment host immune effector mechanisms.
... Although wheat germ is removed as a by-products during milling, it was recently reported to possess potential anti-carcinogenic properties, but its anti-oxidant and anti-adipogenic effects are still unknown (24). We prepared ethanol extracts of wheat germ and wheat germ fermented using Aspergillus oryzae. ...
Most of the wheat germ in cereal grains is removed during the milling process. Various physiological effects have been reported for bioactive substances in wheat germ such as phenolic acids and flavonoids. In this study, the anti-oxidant and anti-adipogenic effects of ethanol extracts from wheat germ (WGE) and wheat germ fermented with Aspergillus oryzae (F-WGE) were investigated in HepG2 and 3T3-L1 cells. The anti-oxidant activity of F-WGE was demonstrated by a dose-dependent increase in the enhanced scavenging capacity of hydroxyl radicals and Cu(2+)-chelating activity compared to WGE. WGE and F-WGE treatment at doses between 10 and 400 μg/mL did not affect the viability of HepG2 and 3T3-L1 cells. Intracellular ROS levels from Cu(2+)-induced oxidative stress were significantly decreased by F-WGE treatment in HepG2 cells compared to WGE. Lipid accumulation was increased in 3T3-L1 adipocytes by 100 μM Fe(2+) treatment, but the accumulation was strongly inhibited by 100 μg/mL of WGE and F-WGE treatment. These results suggest that changes in bioactive substances during the fermentation of wheat germ can potentiate scavenging activities against transition metal-induced oxidative stress and lipid accumulation in 3T3-L1 adipocytes. Therefore, we propose that F-WGE is a novel food materials and provided scientific evidences for its efficacy in the development of functional foods.
