A medical nutriment has supportive value in the treatment of colorectal cancer

Jakab, Ferenc; Shoenfeld, Yehuda; Balogh, Attila; Nichelatti, Michele; Hoffmann, Ann Sophie; Kahán, Zsuzsa; Lapis, K.; Mayer, A.; Sápy, Péter; Szentpétery, F; Telekes, András; Tamás, László; Vágvölgyi, Attila; Hídvégi, Máté

doi:10.1038/sj.bjc.6601153

Cited by 61 publications

(58 citation statements)

References 10 publications

(13 reference statements)

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“…The wheat germ constitutes approximately 2.5% of the total weight of the wheat kernel, the production of FWGE involves fermenting wheat germs of the genus Triticum vulgaris by adding baker's yeast (Saccharomyces cerevisiae) (Hidvégi et al, 1999). Administration of FWGE proved to be effective as supportive therapy to surgery plus chemotherapy for a colorectal cancer patient without any toxic effects (Jakab et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Fermented Wheat Germ Extract on Biochemical, Physiological and Performance Parameters of Broiler Chickens

Ellakany¹,

El-Sayed²,

Soliman³

et al. 2017

AJVS

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Key words:Fermented Wheat Germ Extract, broiler, challenge Fermented wheat germ extract (FWGE) is a multisubstance composition contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects as well as it is a concentrated source of vitamins, minerals, and protein.An experimental trial of FWGE supplementation to broiler feed from one day old with a rate of 0.5, 1.5 and 3 g/kg feed was tried. Results revealed that all doses of FWGE increased body weight significantly (p≤0.05), especially with the dose of 3 g/kg feed. Also, FCR values decreased significantly (p≤0.05) in the FWGE treated groups. Regarding biochemical analysis at 35 days old, the most significant results obtained with the doses of 1.5 and 3 g FWGE/kg feed especially in SGOT, SGPT, creatinine, uric acid, total protein, glucose, and triglycerides levels. Physiologically, FWGE only increased hemoglobin concentration significantly (p≤0.05) without alteration of red blood and white blood cells counts. There was also a significant increase (p≤0.05) in the intestinal weight in relation to carcass weight% and a significant decrease (p≤0.05) in the liver and total body fat weights in relation to carcass weight%. At 45 days (10 days after vNDV challenge), the mortality rates were 60% in the non-treated non-vaccinated challenged chicken group 5 and 4% in the nontreated vaccinated challenged chicken group 4 without appearance of any mortality in the 3 FWGE treated groups. Also, addition of FWGE had a positive effect on HI titers for NDV in the collected serum samples at 45 days old. Finally, it was concluded that FWGE improved the general health condition of broilers regarding biochemical and physiological parameters and immune response to NDV vaccination.

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Section: Introductionmentioning

confidence: 99%

The Effect of Fermented Wheat Germ Extract on Biochemical, Physiological and Performance Parameters of Broiler Chickens

Ellakany¹,

El-Sayed²,

Soliman³

et al. 2017

AJVS

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“…Avemar remarkably inhibits tumor metastasis formation after chemotherapy and surgery in clinically advanced colorectal cancers. Patients receiving standard surgical and chemopreventive therapies for their advanced colorectal cancers developed significantly less new metastases during the 9-month follow-up period when treated with additional 9 g/day Avemar daily (6,7). In a recent randomized clinical study report Avemar significantly prolonged (doubled) time-to-progression in high-risk melanoma patients (8).…”

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confidence: 99%

Fermented Wheat Germ Extract Inhibits Glycolysis/Pentose Cycle Enzymes and Induces Apoptosis through Poly(ADP-ribose) Polymerase Activation in Jurkat T-cell Leukemia Tumor Cells

Comı́n-Anduix

Boros

Marín

et al. 2002

Journal of Biological Chemistry

113

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The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC 50 concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G 1 peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodideand annexin V-stained cells indicated that the growthinhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased 13 C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC 50 (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.The preventive and therapeutic potential of two natural wheat products, wheat bran and fermented wheat germ (Avemar), in experimental carcinogenesis has recently been described (1, 2). Although no chemical constituents are yet isolated and tested experimentally, it is likely that benzoquinones and wheat germ agglutinin in wheat germ and fiber and lipids and phytic acid in wheat bran play a significant role in exerting anti-carcinogenic effects. In a recent report utilizing intracellular carbon flow studies with a 13 C-labeled isotope of glucose and biological mass spectrometry (GC/MS), 1 it was demonstrated that the crude powder of fermented wheat germ dosedependently inhibits nucleic acid ribose synthesis primarily through the nonoxidative steps of the pentose cycle while increasing direct glucose carbon oxidation and acetyl-CoA utilization toward fatty acid synthesis in pancreatic adenocarcinoma cells (3). These metabolic changes indicate that fermented wheat germ exerts its anti-proliferative action through altering metabolic enzyme activities, which primarily control glucose carbon flow toward nucleic acid synthesis.In vivo, Avemar has a marked inhibitory effect on metastasis formation in tumor-bearing animals (4), an...

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“…In addition, the activation of transketolases by application of thiamine stimulates tumour growth (Comin-Anduix et al, 2001). Furthermore, several natural products have been reported to inhibit transketolase enzyme activity in vitro, and also to inhibit cell proliferation or suppress tumour growth in mouse models or cancer patients as a result of reduction of transketolase activity (Hidvegi et al, 1999;Boros et al, 2001a, b;Comin-Anduix et al, 2002;Jakab et al, 2003).…”

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confidence: 99%

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted

et al. 2006

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Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactatebased matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

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A medical nutriment has supportive value in the treatment of colorectal cancer

Cited by 61 publications

References 10 publications

The Effect of Fermented Wheat Germ Extract on Biochemical, Physiological and Performance Parameters of Broiler Chickens

The Effect of Fermented Wheat Germ Extract on Biochemical, Physiological and Performance Parameters of Broiler Chickens

Fermented Wheat Germ Extract Inhibits Glycolysis/Pentose Cycle Enzymes and Induces Apoptosis through Poly(ADP-ribose) Polymerase Activation in Jurkat T-cell Leukemia Tumor Cells

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted

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