Chinese red yeast rice (CRYR) inhibits proliferation and stimulates apoptosis in both COX‐2 expressing and non‐expressing human colon cancer cells via inhibition of cholesterogenesis

Abstract

De novo cholesterogenesis and inflammation are both critical steps in colon carcinogenesis. In population-based studies, statin drug consumption is associated with a reduced risk of colon cancer. Statins are also known to have anti-inflammatory actions which could contribute to their activity in both heart disease and colon cancer prevention. CRYR contains nine Monacolins one of which is lovastatin (MonacolinK). We have studied CRYR in humans demonstrating cholesterol-lowering and have been interested in their potential use for chemoprevention of colon cancer. To determine whether, the primary mechanisms of CRYR in colon cancer was via inhibition of inflammation and/or cholesterogenesis, two human colon cancer cell lines either with (HT-29) or without (HCT-116) expression of cyclooxygenase 2 (COX-2) were treated with CRYR extract (0 to 300 ug/ml) for 24, 48 or 72 h. Cell proliferation and apoptosis were determined using the MTT cell viability assay and TUNEL assay. CRYR treatment (50 ug/ml) for 72 h resulted in 54 % and 44 % of suppression in proliferation in HCT-116 (p<0.001) and HT-29 (p<0.001), respectively. The IC50 on proliferation was 51.6 in HCT-116 and 58.9 in HT-29 cells in the same time point. Apoptosis was enhanced with 48 h incubation of CRYR (100 ug/ml) in both cell lines (p<0.05). The present results demonstrate that CRYR inhibited proliferation and stimulated apoptosis regardless of the expression of COX-2. Studies in transgenic animals and humans will be needed to confirm that CRYR inhibits colon cancer risk primarily via inhibition of de novo cholesterogenesis. Fund: UCLA CNRU CA 42710.