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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract

Authors: Christoph Otto, Theresa Hahlbrock, Kilian Eich, Ferdi Karaaslan, Constantin Jürgens, Christoph-Thomas Germer, Armin Wiegering, Ulrike Kämmerer

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

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Abstract

Background

Fermented wheat germ extract (FWGE) sold under the trade name Avemar exhibits anticancer activity in vitro and in vivo. Its mechanisms of action are divided into antiproliferative and antimetabolic effects. Its influcence on cancer cell metabolism needs further investigation. One objective of this study, therefore, was to further elucidate the antimetabolic action of FWGE. The anticancer compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the major bioactive compound in FWGE and is probably responsible for its anticancer activity. The second objective of this study was to compare the antiproliferative properties in vitro of FWGE and the DMBQ compound.

Methods

The IC50 values of FWGE were determined for nine human cancer cell lines after 24 h of culture. The DMBQ compound was used at a concentration of 24 μmol/l, which is equal to the molar concentration of DMBQ in FWGE. Cell viability, cell cycle, cellular redox state, glucose consumption, lactic acid production, cellular ATP levels, and the NADH/NAD+ ratio were measured.

Results

The mean IC50 value of FWGE for the nine human cancer cell lines tested was 10 mg/ml. Both FWGE (10 mg/ml) and the DMBQ compound (24 μmol/l) induced massive cell damage within 24 h after starting treatment, with changes in the cellular redox state secondary to formation of intracellular reactive oxygen species. Unlike the DMBQ compound, which was only cytotoxic, FWGE exhibited cytostatic and growth delay effects in addition to cytotoxicity. Both cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD+ ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy.

Conclusions

FWGE and the DMBQ compound both induced oxidative stress-promoted cytotoxicity. In addition, FWGE exhibited cytostatic and growth delay effects associated with impaired glucose utilization which led to autophagy, a possible previously unknown mechanism behind the influence of FWGE on cancer cell metabolism.
Appendix
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Literature
1.
Heimbach JT, Sebestyen G, Semjen G, Kennepohl E. Safety studies regarding a standardized extract of fermented wheat germ. Int J Toxicol. 2007;26(3):253–9.CrossRefPubMed
2.
Hidvégi M, Rásó E, Tömösközi-Farkas R, Paku S, Lapis K, Szende B. Effect of Avemar and Avemar + Vitamin C on tumor growth and metastasis in experimental animals. Anticancer Res. 1998;18:2353–8.PubMed
3.
Hidvégi M, Rásó E, Tömösközi-Farkas R, Szende B, Paku S, Prónai L, et al. MSC, a new benzoquinone-containing natural product with antimetastatic effect. Cancer Biother Radiopharm. 1999;14(4):277–89.CrossRefPubMed
4.
Jakab F, Shoenfeld Y, Balogh Á, Nichelatti A, Kahán Z, Lapis K, et al. A medical nutriment has supportive value in the treatment of colorectal cancer. Br J Cancer. 2003;89:465–9.CrossRefPubMedPubMedCentral
5.
Demidov LV, Manziuk LV, Kharkevitch GY, Pirogova NA, Artamonova EV. Adjuvant fermented wheat germ extract (Avemar) nutraceutical improves survival of high risk skin melanoma patients: a randomized pilot phase II clinical study with a 7-year follow-up. Cancer Biother Radiopharm. 2008;23(4):477–82.CrossRefPubMed
6.
7.
Piccart-Gebhart MJ. Anthracyclines and the tailoring of treatment for early breast cancer. N Engl J Med. 2006;354(20):2177–9.CrossRefPubMed
8.
Bachur NR, Gordon SL, Gee MV. A general mechanism of microsomal activation of quinone anticancer agents to free radical. Cancer Res. 1978;38:1745–50.PubMed
9.
Pethig R, Gascoyne PRC, McLaughlin JA, Szent-Györgyi A. Ascorbate-quinone interactions: electrochemical, free radical and cytotoxic properties. Proc Natl Acad Sci U S A. 1983;80:129–32.CrossRefPubMedPubMedCentral
10.
Winterbourn CC. Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol. 2008;4(5):278–86.CrossRefPubMed
11.
12.
13.
Lind C, Hochstein P, Ernster L. DT-diaphorase as a quinone reductase: a cellular control device against semiquinone and superoxide radical formation. Arch Biochem Biophys. 1982;216(1):178–85.CrossRefPubMed
14.
Illmer C, Madlener S, Horvath Z, Saiko P, Losert A, Herbacek I, et al. Immunologic and biochemical effects of the fermented wheat germ extract Avemar. Exp Biol Med. 2005;230:144–9.
15.
Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4(11):891–9.CrossRefPubMed
16.
Verrax J, Vanbever S, Stockis J, Taper H, Calderon PB. Role of glycolysis inhibition and poly(ADP-ribose) polymerase activation in necrotic-like cell death caused by ascorbate/menadione-induced oxidative stress in K562 human chronic myelogenous leukemic cells. Int J Cancer. 2007;120(6):1192–7.CrossRefPubMed
17.
Boros LG, Lapis K, Szende B, Tömösközi-Farkas R, Balogh A, Boren J, et al. Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Pancreas. 2001;23(2):141–7.CrossRefPubMed
18.
Comin-Anduix B, Boros LG, Marin S, Boren J, Callol-Massot C, Centelles JJ, et al. 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. J Biol Chem. 2002;277(48):46408–14.CrossRefPubMed
19.
Saiko P, Ozsvar-Kozma M, Madlener S, Bernhaus A, Lackner A, Grusch M, et al. Avemar, a nontoxic fermented wheat germ extract, induces apoptosis and inhibits ribonucleotide reductase in human HL-60 promyelocytic leukemia cells. Cancer Lett. 2007;250:323–8.CrossRefPubMed
20.
Klingelhoeffer C, Kämmerer U, Koospal M, Mühling B, Schneider S, Kapp M, et al. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress. BMC Complementary and Altern Med. 2012;12:61. doi:10.​1186/​1472-6882-12-61.CrossRef
21.
Huber W, Koella JC. A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites. Acta Trop. 1993;55(4):257–61.CrossRefPubMed
22.
Wiegering A, Korb D, Thalheimer A, Kämmerer U, Allmannritter J, Matthes N, et al. E7080, a multitargeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts. Neoplasia. 2014;16(11):972–81.CrossRefPubMedPubMedCentral
23.
24.
Powis G. Metabolism and reactions of quinoid anticancer agents. Pharmacol Ther. 1987;35(1–2):57–162.CrossRefPubMed
25.
Butler J, Hoey BM. Are reduced quinones necessarily involved in the antitumour activity of quinone drugs? Br J Cancer Suppl. 1987;8:53–9.PubMedPubMedCentral
26.
Kalyanaraman B, Darley-Usmar V, Davies KJ, Dennery PA, Forman HJ, Grisham MB, et al. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med. 2012;52(1):1–6.CrossRefPubMedPubMedCentral
27.
Triton TR, Yee G. The anticancer agent adriamycin can be actively cytotoxic without entering cells. Science. 1982;217(4556):248–50.CrossRefPubMed
28.
29.
Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11(2):85–95.CrossRefPubMed
30.
Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A. 2008;105(48):18782–7.CrossRefPubMedPubMedCentral
31.
Tanida I, Minematsu-Ikeguchi N, Ueno T, Kominami E. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy. 2005;1(2):84–91.CrossRefPubMed
32.
Pérez-Mancera PA, Young AR, Narita M. Inside and out: the activities of senescence in cancer. Nat Rev Cancer. 2014;14(8):547–58.CrossRefPubMed
33.
Cailleau R, Young R, Olivé M, Reeves Jr WJ. Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974;53(3):661–74.PubMed
34.
Deer EL, González-Hernández J, Coursen JD, Shea JE, Ngatia J, Scaife CL, et al. Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 2010;39(4):425–35.CrossRefPubMedPubMedCentral
35.
Vollmers HP, Stulle K, Dämmrich J, Pfaff M, Papadopoulos T, Betz C, Saal K, Müller-Hermelink HK. Characterization of four new gastric cancer cell lines. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63(6):335–43.CrossRefPubMed
36.
Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977;59(1):221–6.PubMed
37.
38.
Tompkins WA, Watrach AM, Schmale JD, Schultz RM, Harris JA. Cultural and antigenic properties of newly established cell strains derived from adenocarcinomas of the human colon and rectum. J Natl Cancer Inst. 1974;52:1101–10.PubMed
Metadata
Title
Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract
Authors
Christoph Otto
Theresa Hahlbrock
Kilian Eich
Ferdi Karaaslan
Constantin Jürgens
Christoph-Thomas Germer
Armin Wiegering
Ulrike Kämmerer
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1138-5

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