Commentary Foodstuffs for Preventing Cancer: The Preclinical and Clinical Development of Berries

Laboratory research involving berries is a promising example of food-based cancer prevention. Berries contain many known chemopreventive agents such as anthocyanins and ellagitannins that can be greatly concentrated in freeze-dried berry powders. Based on our program of berry research, this commentary presents the first reported stepwise scheme for the preclinical and clinical development of foodstuffs for cancer prevention. Our preclinical work within this scheme includes promising approaches for assessing the chemopreventive potential of berry powder and berry extracts in preclinical model systems, for determining the mechanisms of action of these agents, and for identifying the active constituents in berries. The commentary also presents preliminary results of clinical trials in the oral cavity, esophagus, and colon using various formulations of freeze-dried berries. The relative merits of berry powders, extracts, or individual constituents (anthocyanins) for cancer prevention are also discussed. Chemoprevention is the administration of one or more chemical entities, either as individual drugs or as dietary supplements, to prevent the initiation of premalignant lesions or their progression to cancer or cancer recurrence (1). Most chemoprevention studies have been conducted with individual compounds including various nutrients and nonnutrient phytochemicals. Our laboratory has devoted considerable effort in the past toward developing individual compounds for cancer prevention, especially the nonnutrient phytochemicals ellagic acid and phenylethyl isothiocyanate (2, 3). Recently, however, we have devoted most of our effort to developing and applying a “food-based” approach to cancer prevention using freeze-dried, commercially available, edible berries. Our approach to evaluating the efficacy of whole berries (containing numerous compounds) for cancer prevention is nearly identical to that used by chemoprevention scientists working with individual compounds. Our interest in berries stemmed from early studies with ellagic acid, which is found in the pulp and seeds but not in the juice of berries (4). Because water accounts for ∼85% to 90% of the wet weight of berries, we reasoned that the removal of water from berries would result in an ∼10-fold concentration of the ellagic acid. Therefore, we began to freeze-dry berries under anoxic conditions to ensure the integrity of their components and to grind the dried berries into powder. Chemical analysis of different berry powders revealed that berries contain multiple chemopreventive agents in addition to ellagic acid (5). Table 1 presents a list of some potential chemopreventive agents in black raspberries (BRB). Blackberries, strawberries, blueberries, and others contain chemopreventive agents similar to those in BRBs (Table 1) but differing in quality and/or quantity. Therefore, berry powders contain a combination of chemoprotective agents that might be expected to act at multiple stages in the carcinogenesis process. This is undoubtedly the case for other foodstuffs as well. Indeed, we were encouraged to test berry powder by early reports on the chemopreventive potential of other foodstuffs such as tea (6, 7), broccoli (8), tomato juice (9), and soybeans (10). This commentary presents a concise summary of current laboratory work with BRBs and discusses several important topics not detailed in previous reviews as well (11–13). It details a stepwise scheme for assessing the chemopreventive potential of berries and other foodstuffs in preclinical models and clinical trials. It is important to mention that this approach has involved the integrative efforts of numerous basic scientists, physician and dental scientists and practitioners, statisticians, laboratory and clinical trial managers and technicians, postdoctoral trainees, and graduate students. I also discuss the potential advantages and disadvantages of powders, extracts, and individual compounds, including related issues of different formulations and routes of administration; the updated status of clinical BRB trials, including the final polyp-regression results of our trial in familial adenomatous Author's Affiliation: Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, Ohio Received 12/4/2008; revised 1/29/2009; accepted 2/2/2009; published OnlineFirst 3/3/09. Grant support: NIH R01 grants CA096130 and CA103180 and U.S. Department of Agriculture grants 38903-03560 and 38903-19245 to the Ohio Agricultural Research and Development Center. Requests for reprints: Gary D. Stoner, Department of Internal Medicine, The Ohio State University, Innovation Centre, 2001 Polaris Parkway, Columbus, OH 43240. Phone: 614-293-3268; E-mail: [email protected]. ©2009 American Association for Cancer Research. doi:10.1158/1940-6207.CAPR-08-0226 1 Unpublished data. 187 Cancer Prev Res 2009;2(3) March 2009 www.aacrjournals.org Published Online First on March 3, 2009 as 10.1158/1940-6207.CAPR-08-0226 Cancer Research. on June 16, 2017. © 2009 American Association for cancerpreventionresearch.aacrjournals.org Downloaded from Published OnlineFirst March 3, 2009; DOI: 10.1158/1940-6207.CAPR-08-0226