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 IC50 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-G1 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 13C 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 IC50
(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