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

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 IC
-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 IC
of 0.042 mg/ml. Furthermore,
-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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