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

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.

Characterizing the Efficacy of Fermented Wheat Germ Extract Against Ovarian Cancer and Defining the Genomic Basis of Its Activity

“…Our findings, related to FWGE activity in OVCA, are consistent with those of Mueller et al 7 , who demonstrated FWGE activity against a single ovarian cancer cell line, A2780. Our data demonstrated that A2780 (and Chi) exhibits the highest levels of FWGE sensitivity.…”

“…6 FWGE has been evaluated in vitro and shown to induce apoptosis in many cancer cell types, including leukemia, melanoma, breast, colon, testicular, head and neck, cervical, ovarian, gastric, thyroid, and brain carcinomas. 7–9 Observations from human clinical trials suggest beneficial effects of FWGE on disease progression and survival in patients with melanoma 10 and colorectal cancer. 11 …”

“…Mueller et al demonstrated FWGE in vitro activity against a single OVCA cell line, A2780, but did not investigate how FWGE interacts with cytotoxic agents against OVCA cells. 7 …”

Mechanism of the anti-angiogenic effect of Avemar on tumor cells

“…Furthermore, Avemar was reported to be an effective adjuvant agent in cancer treatment for several types of cancer. such as breast, colon, lung and prostate cancer (11). However, the mechanism of the anti-angiogenic effect of Avemar is unclear.…”

“…Numerous studies have investigated cytotoxic effects of Avemar on nearly all types of cancers that's why we did not do any cell viability in this project. Therefore, the Avemar concentrations were determined according to the literature (11)(12)(13)(14). The main aim of the present study was to determine the effects of Avemar on angiogenesis.…”