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Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract
Christoph Otto1,2, Theresa Hahlbrock3,4, Kilian Eich3,5
1Experimental Surgery, Department of General, Visceral, Vascular, and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Str. 6, D-97080, Würzburg, Germany. Otto_c@ukw.de.
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.
Insights
Fermented wheat germ extract (FWGE) shows anticancer effects by inducing oxidative stress and impairing glucose metabolism, leading to cell death and growth delay. FWGE also triggers autophagy, a novel mechanism in its metabolic influence on cancer cells.
Area of Science:
- Oncology
- Cancer Metabolism
- Pharmacology
Background:
- Fermented wheat germ extract (FWGE) demonstrates in vitro and in vivo anticancer properties.
- FWGE's mechanisms include antiproliferative and antimetabolic effects, with its influence on cancer cell metabolism requiring further investigation.
- 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the primary bioactive compound in FWGE, likely responsible for its anticancer activity.
Purpose of the Study:
- To further elucidate the antimetabolic action of FWGE.
- To compare the in vitro antiproliferative effects of FWGE and DMBQ.
Main Methods:
- Determined IC50 values of FWGE for nine human cancer cell lines.
- Measured cell viability, cell cycle, redox state, glucose consumption, lactic acid production, ATP levels, and NADH/NAD(+) ratio.
- Utilized DMBQ at a concentration equivalent to its molar concentration in FWGE.
Main Results:
- FWGE (10 mg/ml) and DMBQ (24 μmol/l) induced significant cell damage and oxidative stress within 24 hours.
- FWGE exhibited both cytotoxic and cytostatic/growth delay effects, while DMBQ was solely cytotoxic.
- FWGE's cytostatic and growth delay effects were linked to impaired glucose utilization, affecting cell cycle, ATP levels, and NADH/NAD(+) ratio.
Conclusions:
- Both FWGE and DMBQ promote cytotoxicity via oxidative stress.
- FWGE demonstrates cytostatic and growth delay effects linked to impaired glucose metabolism, potentially through autophagy.
- Autophagy may represent a novel mechanism underlying FWGE's impact on cancer cell metabolism.
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