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

Judson, Patricia L. MD*†; Al Sawah, Entidhar MD*†; Marchion, Douglas C. PhD*†; Xiong, Yin PhD*†; Bicaku, Elona MBA*†; Zgheib, Nadim Bou MD*; Chon, Hye Sook MD*; Stickles, Xiaomang B. MD*; Hakam, Ardeshir MD; Wenham, Robert M. MD*†; Apte, Sachin M. MD*; Gonzalez-Bosquet, Jesus MD*; Chen, Dung-Tsa PhD§; Lancaster, Johnathan M. MD, PhD*†

International Journal of Gynecological Cancer: July 2012 - Volume 22 - Issue 6 - p 960–967
doi: 10.1097/IGC.0b013e318258509d
Basic Science

Objective: Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.

Methods: In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level.

Results: We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity.

Conclusions: Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE’s effect on human cancer cells.

Research Highlights:

* Fermented wheat germ extract has significant antiproliferative effects on OVCA cell lines and may enhance the effect of cisplatin-induced cell death.

* Genome-wide expression data reveal that FWGE sensitivity in ovarian cancer cells was associated with 2142 genes, representing 27 biologic pathways.

* The known safety and tolerability of FWGE supports the clinical evaluation of this natural product in patients with ovarian cancer.

*Department of Women’s Oncology, †Experimental Therapeutics Program, ‡Department of Anatomic Pathology, and §Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Address correspondence and reprint requests to Johnathan M. Lancaster, MD, PhD, GYN PROG MCC3057 Department of Women’s Oncology, Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL 33612. E-mail: Johnathan.Lancaster@Moffitt.org.

Drs Judson and Al Sawah contributed equally to this work.

This project was supported in part by the Moffitt Cancer Center Merit Society, the National Cancer Institute (grant R21 CA-110499-01A2), the Ocala Royal Dames For Cancer Research, Inc, the Phi Beta Psi Sorority, the Hearing the Ovarian Cancer Whisper, Jacquie Liggett Foundation, the Ovarian Cancer Research Fund, and the US Army Medical Research and Materiel Command under award no. DAMD17-02-2-0051.

Dr Judson was supported by a grant from the Merit Society to her institution. Dr Apte was part of the advisory board for Genentech. Dr Lancaster has a pending grant support to the institution from Avemar and is part of the speaker’s bureau of Amgen and Orthobiotech. All other authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

Received February 21, 2012

Accepted March 31, 2012

Copyright © 2012 by IGCS and ESGO