Enantiomeric gossypol (GP), a polyphenolic pigment that occurs naturally in cotton, exists as an enantiomeric mixture at a 3:2 ratio of (+)-GP to (-)-GP). Cottonseed meal (CSM) is a protein supplement in poultry feeds. We have demonstrated that (-)-GP possesses potent demethylating activity and may serve as a novel small molecule in food to re-activate silenced cancer suppressor genes for improved therapeutic efficacy in human breast cancer patients. Gossypol\#8217;s anticancer potential as a novel bio-active chemopreventive food component or therapeutic agent merits further basic research to explore this low cost and abundant natural agricultural product. Thus, we hypothesize that anti-breast cancer meat and eggs can be produced by feeding layer hens (-)-GPCSM. To test this hypothesis we employed both in vitro and in vivo models to determine the successful development of meat and eggs with anti-cancer potential from layer hens. Laying hens were fed experimental diets containing 0, 8, 16 and 32 ppm (-)-GP. Feed intake, egg production, and egg yolk discoloration were monitored. We tested sera from chickens fed (-)-GP enriched diets on the proliferation of MCF-7 cells. Culture medium containing 2.5% and 12.5% sera from chickens fed (-)-GP enriched diets significantly suppressed the proliferation of MCF-7 cells after 24 hrs exposure. To determine toxicity of GP to chickens, we measured LDH in sera. Limited hepatic toxicity was observed from the liver LDH test. It is known that GP covalently binds to a variety of proteins and it is generally accepted that protein bound GP is biologically inactive. To challenge this concept, we covalently bound (-)-GP with the chicken meat specific structural protein, myosin. Subsequently, MCF-7 cells were incubated with 0, 2, 4 \#956;M of chicken myosin bound-(-)-GP and pure (-)-GP for 24 hr @ 37 o C. Treatment with (-)-GP at 2 and 4 µM significantly suppressed the proliferation of MCF-7 cells. The chicken myosin-bound (-)-GP had an inhibitory effect on MCF-7 cell proliferation at 4 µM. This observation demonstrates that myosin bound (-)-GP is biologically active although at a lesser potency in vitro than the pure free (-)-GP.Finally, we recently developed a (-)-GP polyclonal antibody in our laboratory to measure (-)-GP in the biological samples harvested from layer hens fed with (-)-GPCSM. We are actively working on developing a sensitive ELISA assay for evaluation of biological samples and an HPLC method for validation of (-)-GP content in these tissues. These data support our hypothesis that the (-)-GP enantiomer bound to meat and egg proteins from the (-)-GPCSM fed layers is biologically active and may aid in protecting healthy and human breast cancer patients. Development of such a value added agricultural product for human consumers is important for better human health. (Supported by Cotton Inc.)

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 952.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO