Effects of black raspberries on cellular and epigenetic biomarkers of colon cancer development in humans

Colorectal cancer (CRC) is the leading digestive tract cancer in the Western world, particularly in the United States where it accounts for approximately 10% of all cancer deaths. The multistage development of CRC is associated with chromosomal instability, DNA-repair defects, aberrant DNA methylation, and mutational events in oncogenes and tumor suppressor genes. Preclinical studies using cultured human colon tumor cells and animal models of colorectal cancer indicate that black raspberries (BRBs) and their constituent anthocyanins and ellagitannins elicit chemopreventive effects against CRC. A 7-day Phase I trial indicated that BRBs are well tolerated by humans and their component anthocyanins and ellagic acid are absorbed into blood. The results of a Phase Ib trial in which BRBs were administered daily to colorectal cancer patients from the time of diagnosis of the disease until surgical removal of the tumor (average = 3 weeks) are presented in this chapter. BRB treatment resulted in reduced proliferation and increased apoptosis of CRC cells. In addition, tumor angiogenesis was inhibited by berries. BRB treatment reduced β-catenin expression and enhanced E-cadherin expression in CRC indicating a protective effect on the Wnt signaling pathway. DNA methylation assays showed that BRBs are capable of demethylating tumor suppressor genes associated with the Wnt pathway, in part, through inhibiting the expression of DNMT1, a DNA methyltransferase that is commonly overexpressed in CRC. These data suggest that BRBs should be further examined for chemopreventive effects against CRC.