Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review, we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on a number of features that define their predictive power for the prevention or progression of cancer.

Access to a wealth of information on the internet has led many cancer patients to use complementary methods as an adjunct to traditional therapy for cancer, with, and more often, without informing their primary caregiver. Of the common complementary modalities, the use of dietary supplements appears to be highly prevalent in patients in active treatment for cancer, and later in cancer survivors. Emerging research suggests that some plant-based agents may, indeed, impact late-stage cancer, influencing molecular processes corrupted by tumor cells to evade detection, expand clonally, and invade surrounding tissues. The intent of this article is to review some of the current science underpinning the use of nutraceuticals in the latter stages of cancer.

A53 Research suggests strong correlations between the inflammation process and colon cancer progression, making it an attractive target for anti-inflammatory drugs and compounds. Muscadines (Vitis rotundifolia), a grape species native to the Southeastern United States, are rich in polyphenols containing many biologically important flavonoids that may have potential anti-inflammatory and anti-oxidant properties. Current research has shown that the muscadine grape has a higher total phenolic and flavonoid content than commercially available red grapes. A hallmark of progressive colon cancers is disruption of different signaling pathways leading to increased proliferation and escape from apoptotic mechanisms. We hypothesize that extracts containing high levels of biologically important polyphenols from the muscadine pomace would induce cell cycle arrest and apoptosis in HT-29 and HT-15 colon cancer cell lines. Polyphenolic compounds were extracted from muscadine pomace using 80% methanol in 6N hydrochloric acid at 60ºC. Whole concentrated extract (WCE) was fractionized using an Oasis HLB column to yield three different muscadine fractions (MF). We compared the cytotoxic effects of both cell lines when treated with WCE versus three different muscadine fractions (MF-1, MF-2, and MF-3). Cell proliferation assays showed a decrease in viable cell proliferation in both cell lines treated with MF-3. Apoptosis was confirmed through the use of flow cytometry and we found evidence of G1 arrest in MF-3 treated cells. Immunoblots for apoptosis-related proteins suggest apoptotic activation of the caspase-3 pathway in treated cells compared to non-treated cells. We conclude that extracts of muscadine grape contain biologically active polyphenols that inhibit the growth of HT-29 and HT-15 colon cancer cells via an apoptotic pathway. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A53.