A purified, fermented, extract of Triticum aestivum has lymphomacidal activity mediated via natural killer cell activation

Abstract

Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the disease. Many patients explore less toxic alternative therapeutics proposed to boost anti-tumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented wheat germ. Fermented wheat germ extract was produced by fermenting wheat germ with Saccharomyces cerevisiae. A protein fraction was tested for lymphomacidal activity in vitro using NHL cell lines and in vivo using mouse xenografts. Mechanisms of action were explored in vitro by evaluating apoptosis and cell cycle and in vivo by immunophenotyping and measurement of NK cell activity. Potent lymphomacidal activity was observed in a panel of NHL cell lines and mice bearing NHL xenografts. This activity was not dependent on wheat germ agglutinin or benzoquinones. Fermented wheat germ proteins induced apoptosis in NHL cells, and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation and production of IFNγ. Fermented wheat germ extract can be easily produced and is efficacious in a human lymphoma xenograft model. The protein fraction is quantifiable and more potent, shows direct pro-apoptotic properties, and enhances immune-mediated tumor eradication. The results presented herein support the novel concept that proteins in fermented wheat germ have direct pro-apoptotic activity on lymphoma cells and augment host immune effector mechanisms.

The Effects of Adjuvant Fermented Wheat Germ Extract on Cancer Cell Lines: A Systematic Review

“…After duplicates were removed, 20 studies were identified as acceptable for full-text evaluation and their full texts were read. At the end of the selection process, 16 articles [ 13 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ] were included in qualitative analysis, while four [ 9 , 17 , 35 , 36 ] were excluded for not complying with inclusion criteria.…”

“…All sixteen studies selected for the review were in-vitro studies published in English. The effects of FWGE were investigated on the following cell lines: Jurkat leukemic T cells were studied by three studies [ 18 , 21 , 32 ] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis; Lymphoma cells were subjected to the treatment and the effects investigated by three studies [ 21 , 27 , 32 ] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects; Gastric cancer cell line experiments reported in three papers [ 22 , 25 , 26 ] found antiproliferative, cytotoxic, cytostatic, and growth-delay effects; Ovarian cancer cell lines, when subjected to treatment with AVEMAR, showed cytotoxic effects [ 23 ], antiproliferative activity [ 25 ], and suppression of cell proliferation [ 29 ]; Breast cancer cell lines appeared to undergo cytotoxicity and apoptosis [ 24 , 25 , 26 , 32 ], while, in one study [ 33 ] investigating the combined administration of AVEMAR and cytostatics, the treatment with AVEMAR resulted in no increase or decrease of cell viability compared to untreated cells; When applied to colon cancer cell lines, FWGE showed antiproliferative activity [ 25 ], cytotoxicity, cytostasis, and induction of cell apoptosis [ 31 ]; The treatment of hepatic cancer cells appeared to cause cytotoxicity, apoptosis [ 32 ], and an inhibition of proliferation [ 25 , 28 ]; Other types of cell lines investigated in the included studies were prostate cancer cells, endocervical adenocarcinoma [ 22 ], cervical epidermoid carcinoma cells [ 25 ], testicular cancer cell lines [ 25 ], head and neck cancer [ 25 ], thyroid and pancreatic cancer cells [ 13 ], melanoma, hepatoma, glioblastoma, neuroblastoma [ …”

“…Jurkat leukemic T cells were studied by three studies [ 18 , 21 , 32 ] and the treatment resulted in cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis;…”

“…Lymphoma cells were subjected to the treatment and the effects investigated by three studies [ 21 , 27 , 32 ] showed growth inhibition, induction of apoptosis, antiproliferation, and cytotoxic effects;…”

Harnessing Microbes for Sustainable Development: Food Fermentation as a Tool for Improving the Nutritional Quality of Alternative Protein Sources

“…Furthermore, plant protein extracts could potentially be further processed to added-value products or pharmaceuticals [171,172], and fermentation processes may serve as instruments to increase tailored health-supporting bioactivities. As an example, a wheat germ protein extract fermented with baker's yeast has been found effective in reducing tumors related with non-Hodgkin lymphoma in an immunodeficient mouse model, probably via a natural killer cell regulated antitumor mechanism [173].…”