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Promising cytotoxic activity profile of fermented wheat germ extract (AvemarĀ®) in human cancer cell lines.

Mueller T, Jordan K, Voigt W - J. Exp. Clin. Cancer Res. (2011)

Bottom Line: 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.The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml.However, sequential drug exposure of 5-FU and FWGE in colon cancer cell lines appeared to be schedule-dependent (5-FU may precede FWGE).Further evaluation of FWGE as a candidate for clinical combination drug regimens appeared to be warranted.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Halle, Department Internal Medicine, Oncology/Hematology and Hemostaseology, Ernst-Grube Str, 40, 06120 Halle/Saale, Germany.

ABSTRACT
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 further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA). Apoptosis was detected by DNA gel electrophoresis.FWGE induced apoptosis and exerted significant antitumor activity in a broad spectrum of 32 human cancer cell lines. The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml. Furthermore, IC50-range was very narrow ranging from 0.3 mg/ml to 0.54 mg/ml in 8 colon cancer cell lines. At combination experiments in colon cancer cell lines when FWGE was simultaneously applied with either 5-FU, oxaliplatin or irinotecan we observed additive to synergistic drug interaction, particularly for 5-FU. At sequential drug exposure with 5-FU and FWGE the observed synergism was abolished.Taken together, FWGE exerts significant antitumor activity in our tumor model. Simultaneous drug exposure with FWGE and 5-FU, oxaliplatin or irinotecan yielded in additive to synergistic drug interaction. However, sequential drug exposure of 5-FU and FWGE in colon cancer cell lines appeared to be schedule-dependent (5-FU may precede FWGE).Further evaluation of FWGE as a candidate for clinical combination drug regimens appeared to be warranted.

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Induction of apoptosis by FWGE. A representative panel of human tumor cell lines was treated with an IC90 of FWGE for 48 h and floating cells were harvested by centrifugation for DNA extraction. DNA was seperated by DNA gel electrophoresis and stained with ethidium bromide subsequently. Typical DNA laddering indicative for apoptosis was visualized by UV light illumination.
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Figure 2: Induction of apoptosis by FWGE. A representative panel of human tumor cell lines was treated with an IC90 of FWGE for 48 h and floating cells were harvested by centrifugation for DNA extraction. DNA was seperated by DNA gel electrophoresis and stained with ethidium bromide subsequently. Typical DNA laddering indicative for apoptosis was visualized by UV light illumination.

Mentions: In order to distinguish the mode of cell death induced by FWGE we treated a representative panel of human cancer cell lines with an IC90 of FWGE for 48 h. Subsequent to treatment, floating cells were harvested and an DNA gel electrophoresis was performed. Clearly, in all treated cell lines the typical 180 bp DNA laddering structure indicative for specific DNA degradation during the process of apoptosis could be detected (Figure 2).


Promising cytotoxic activity profile of fermented wheat germ extract (AvemarĀ®) in human cancer cell lines.

Mueller T, Jordan K, Voigt W - J. Exp. Clin. Cancer Res. (2011)

Induction of apoptosis by FWGE. A representative panel of human tumor cell lines was treated with an IC90 of FWGE for 48 h and floating cells were harvested by centrifugation for DNA extraction. DNA was seperated by DNA gel electrophoresis and stained with ethidium bromide subsequently. Typical DNA laddering indicative for apoptosis was visualized by UV light illumination.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104483&req=5

Figure 2: Induction of apoptosis by FWGE. A representative panel of human tumor cell lines was treated with an IC90 of FWGE for 48 h and floating cells were harvested by centrifugation for DNA extraction. DNA was seperated by DNA gel electrophoresis and stained with ethidium bromide subsequently. Typical DNA laddering indicative for apoptosis was visualized by UV light illumination.
Mentions: In order to distinguish the mode of cell death induced by FWGE we treated a representative panel of human cancer cell lines with an IC90 of FWGE for 48 h. Subsequent to treatment, floating cells were harvested and an DNA gel electrophoresis was performed. Clearly, in all treated cell lines the typical 180 bp DNA laddering structure indicative for specific DNA degradation during the process of apoptosis could be detected (Figure 2).

Bottom Line: 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.The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml.However, sequential drug exposure of 5-FU and FWGE in colon cancer cell lines appeared to be schedule-dependent (5-FU may precede FWGE).Further evaluation of FWGE as a candidate for clinical combination drug regimens appeared to be warranted.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Halle, Department Internal Medicine, Oncology/Hematology and Hemostaseology, Ernst-Grube Str, 40, 06120 Halle/Saale, Germany.

ABSTRACT
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 further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA). Apoptosis was detected by DNA gel electrophoresis.FWGE induced apoptosis and exerted significant antitumor activity in a broad spectrum of 32 human cancer cell lines. The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml. Furthermore, IC50-range was very narrow ranging from 0.3 mg/ml to 0.54 mg/ml in 8 colon cancer cell lines. At combination experiments in colon cancer cell lines when FWGE was simultaneously applied with either 5-FU, oxaliplatin or irinotecan we observed additive to synergistic drug interaction, particularly for 5-FU. At sequential drug exposure with 5-FU and FWGE the observed synergism was abolished.Taken together, FWGE exerts significant antitumor activity in our tumor model. Simultaneous drug exposure with FWGE and 5-FU, oxaliplatin or irinotecan yielded in additive to synergistic drug interaction. However, sequential drug exposure of 5-FU and FWGE in colon cancer cell lines appeared to be schedule-dependent (5-FU may precede FWGE).Further evaluation of FWGE as a candidate for clinical combination drug regimens appeared to be warranted.

Show MeSH
Related in: MedlinePlus