A Fermented Wheat Germ Extract Contains Protein Components Active against NSCLC Xenografts In Vivo

Abstract

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the need remains for non-toxic, effective NSCLC therapies, especially in an elderly patient population. Our lab has previously identified a protein fraction from the nutraceutical Avemar^®-dubbed fermented wheat germ protein (FWGP)-with demonstrated efficacy in lymphoma models both in vitro and in vivo. Here, we show that FWGP also has anti-tumor activity in vitro and in vivo against lung cancer. In vitro cytotoxicity against multiple lung cancer cell lines yielded IC₅₀ values comparable to those previously established with the parent product, Avemar. Further, significant A549 xenograft growth inhibition occurred in athymic nu/nu mice receiving FWGP in both pre-radiated and non-radiated models when compared to the untreated control. Encouragingly, mice treated with FWGP experienced no toxicities as detected by weight reduction or blood chemistry analysis. These data support the further study of FWGP as a potential non-toxic therapy for lung cancer and other oncologic indications.

Keywords: A549; fermented wheat germ extract; fermented wheat germ protein (FWGP); natural product; non-small cell lung cancer (NSCLC); non-toxic.

Figure 1

In vivo efficacy of FWGE and FWGP without pre-treatment irradiation. (A) A549 cells were implanted in nu/nu mice on both flanks of each mouse without radiation. Mice (n = 8 animals/group) were treated with either Avemar (FWGE) 3 g/kg gavage or FGWP 1.4 g/kg gavage 5 days/week for 8 weeks. (B) Body weight was measured to monitor possible toxicity throughout the study. Data represent the average ± standard error of the mean (SEM) of tumor volumes, (n = 16 tumors/group) as analyzed via ANOVA with Holm–Sidak multiple comparison. Statistical significance is indicated as ** p < 0.01.

Figure 2

Blood samples were taken from 5 mice per treatment group at the end of the 84-day study and analyzed by the UC Davis Department of Comparative Pathology at the School of Veterinary Medicine. Error bars represent the standard deviation from the mean.

Figure 3

In vivo model of FWGE and FWGP with pre-implantation radiation. A549 tumors were established in nu/nu mice after receiving radiation (400 rad) on both flanks of each mouse, providing a total of 14 tumors for each experimental group. Data represent the averaged tumor volumes ± SEM for each mouse (n = 7 animals/group, ANOVA with Holm–Sidak multiple comparison). Statistical significance is indicated as * p < 0.05, ** p < 0.01.