Anti‐proliferative Effect of Curcumin is Mediated by Down‐regulation of Polycomb Complex Protein, BMI1

Abstract

BMI1 encodes a 37‐kDa protein that is a key regulatory component of PRC1 (polycomb regulatory complex‐1). BMI1 functions as an oncogene, induces cell growth and promotes tumor growth in in vitro and in vivo animal models. BMI1 is currently recognized as a gene of interest in terms of pharmaceutical drug development. Curcumin, a major phytochemical in turmeric, inhibits the proliferation of many types of cancer cells, both in vitro and in vivo. Previously, we observed that DLD‐1 colorectal cancer cells had a suppressed BMI1 expression following curcumin treatment. In addition, there was an inhibition of cell proliferation. This statistically significant finding indicates that curcumin potentially inhibits DLD‐1 cell proliferation by targeting BMI1. Curcumin has potential to be used in colorectal cancer cell therapy, however, it has been reported to have poor bioavailability. The purpose of this study is to determine whether or not modified curcumin compounds (dimethoxycurcumin, bisdemethoxycurcumin) and curcumin metabolite (tetrahydrocurcumin), with a higher bioavailability, have the same mechanism of action as curcumin in DLD‐1 colorectal cancer cells. DLD1 cells were treated with curcumin, dimethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin. After 48 hours, BMI1 gene expression and protein levels will be measured. Preliminary results suggested that dimethoxycurcumin reduced BMI1 protein expression more than curcumin.Support or Funding InformationTAA and KS are supported by the DeNardo Education and Research Foundation.