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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.

SUBMITTER: Levis DJ

PROVIDER: S-EPMC10530145 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Levis Daniel J DJ Meckler Joshua F JF O'Donnell Robert T RT Tuscano Joseph M JM

Current issues in molecular biology 20230825 9

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<sup>®</sup>-dubbed fermented wheat germ ...[more]

PMID: 37754232

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Project description:Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and ?-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362?±?0.05 and 2.11?±?0.02?mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763?±?0.05 and 3.795?±?0.03?mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331?±?0.04 and 3.971?±?0.02?mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 ?g/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1?mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1?mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.

Project description:Treatment of 1 microM wheat-germ aspartate transcarbamoylase with 1 mM-pyridoxal 5'-phosphate caused a rapid loss of activity, concomitant with the formation of a Schiff base. Complete loss of activity occurred within 10 min when the Schiff base was reduced with a 100-fold excess of NaBH4. Concomitantly, one amino group per chain was modified. No further residues were modified in the ensuing 30 min. The kinetics of inactivation were examined under conditions where the Schiff base was reduced before assay. Inactivation was apparently first-order. The pseudo-first-order rate constant, kapp., showed a hyperbolic dependence upon the concentration of pyridoxal 5'-phosphate, suggesting that the enzyme first formed a non-covalent complex with the reagent, modification of a lysine then proceeding within this complex. Inactivation of the enzyme by pyridoxal was 20 times slower than that by pyridoxal 5'-phosphate, indicating that the phosphate group was important in forming the initial complex. Partial protection against pyridoxal phosphate was provided by the leading substrate, carbamoyl phosphate, and nearly complete protection was provided by the bisubstrate analogue, N-phosphonoacetyl-L-aspartate, and the ligand-pair carbamoyl phosphate plus succinate. Steady-state kinetic studies, under conditions that minimized inactivation, showed that pyridoxal 5'-phosphate was also a competitive inhibitor with respect to the leading substrate, carbamoyl phosphate. Pyridoxal 5'-phosphate therefore appears to be an active-site-directed reagent. A sample of the enzyme containing one reduced pyridoxyl group per chain was digested with trypsin, and the labelled peptide was isolated and shown to contain a single pyridoxyl-lysine residue. Partial sequencing around the labelled lysine showed little homology with the sequence surrounding lysine-84, an active-centre residue of the catalytic subunit of aspartate transcarbamoylase from Escherichia coli, whose reaction with pyridoxal 5'-phosphate shows many similarities to the results described in the present paper. Arguably the reactive lysine is conserved between the two enzymes whereas the residues immediately surrounding the lysine are not. The same conclusion has been drawn in a comparison of reactive histidine residues in the two enzymes [Cole & Yon (1986) Biochemistry 25, 7168-7174].

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

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

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