Abstract B71: Phellodendron bioactive molecule (PBM): A potential natural agent for prevention of colon cancer

Abstract

Abstract PBM is a yellow colored compound isolated from extracts of Phellodendron species. In the current study, PBM was subjected to understand the effect on colon cancer using human cancer cell lines. The activity was studied using three cancer cells having different degree if malignancy induction namely, SW-480, HT-29 and Caco-2 cells. The colon fibroblast (112CoN) cells, which are non cancerous were used to understand the toxicity of compound. The cell viability assay of PBM demonstrated both dose and time dependent activity in all the cells. This naturally occurring compound was found be effective after 24 h of treatment (IC50 value at 12 h was more than 75 µM) showing minimum IC50 against SW-480, which was 24, 16 and 5 µM at 24, 48 and 72 h, respectively. The IC50 was in the range of 42–50 µM for HT-29 cells and 18–53 µM for Caco-2 cells. Furthermore, the toxicity to normal cell was not significant indicating the non-toxicity compound at 100 µM in the model. Treatment at 10 µM has shown induction of aneuploidy (35±2% of cells) in SW-480 cells and treatment at 25 and 10 µM has increased accumulation of cells in G0/G1 phase. Protein expression results suggest that, PBM is capable of inhibiting cancer through inducing caspases dependant apoptosis in case of SW-480 cells. The inhibition was also found to be through inhibiting inflammatory proteins. Both the apoptosis and anti-inflammatory activity were higher at 48 and 72 h of treatment. Result of the current study provides an evidence for inhibition of colon cancer by PBM through multiple targets such as cell cycle arrest, apoptosis and inhibition of inflammation. In summary, PBM may be an ideal compound to be considered for in vivo studies to explore its application in colon cancer prevention. This project is based upon work supported by the USDA-CSREES # 2009-34402-19831 “Designing Foods for Health” through the Vegetable and Fruit Improvement Center. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B71.