1. Introduction

Recently, more and more attention has been placed on the use of nutraceuticals as therapeutic

agents for cancer prevention, as well as supplements to conventional therapy because of their promising

effects and a low rate of toxicity [1–3]. A number of natural compounds have been found to inhibit one

or more pathways that contribute to proliferation of cancer cells and metastatic processes [4]. The most

investigated and promising compounds studied in the last years include: curcumin [5], resveratrol [6],

and indole-3-carbinol [7], which are naturally present in some species of fruit and vegetables.

Fermented wheat germ extract (FWGE; trade name AVEMAR) is a product of industrial

fermentation of wheat germ. Its production process is patented and is derived from the extraction of

wheat germ and fermentation by Saccharomyces cerevisiae, followed by separation of the fermentation

liquid, drying, and then granulation. As with other nutraceuticals, FWGE contains various molecules,

but recent studies assume that the two quinones, 2-methoxy benzoquinone and 2, 6-dimethoxy

benzoquinone, which are present in wheat germ as glucosides, are likely to be responsible for some of

the biological properties of FWGE [8,9].

Quinones are cyclic organic compounds containing two carbonyl groups (C=O) linked to the

cyclic structure of a conjugated system. Several anticancer compounds, e.g., Mitomycin C, Mitotraxan,

Doxorubicin, and Daunorubicin, are quinone derivatives [10,11]. The anticancer characteristics of

AVEMAR have been deeply investigated, and results have suggested its metabolic, antiproliferative,

and antimetastatic effects [12–14].

The antimetabolic effects of FWGE on cancer cells seems to be due to a hypermetabolic state of

the cancer cells and their upregulated utilization of glucose [15,16]. The antimetastatic effect of FWGE,

besides the immune-reconstitution, may also be due to its cell adhesion inhibitory, cell proliferation

inhibitory, apoptosis enhancing, and antioxidant characteristics, which have also been observed in

some in vitro experiments [17]. The antiproliferative action has been investigated in in vitro and

in vivo studies performed on various human cancer cell lines and animal models, and results have

shown a reduction of tumor growth in a dose-dependent manner [8,17–19].

The antimetastatic effect of FWGE investigated in vitro and in vivo by several studies appears to

be promising for FWGE to be used alone or in association with traditional anticancer agents [8,17].

The aim of this systematic review is to summarize the data available in the scientific literature

concerning the in vitro activity of FWGE on malignant cells.

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