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Open Access Highly Accessed Research article

New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

Ling Cen1, Brian Hutzen12, Sarah Ball12, Stephanie DeAngelis1, Chun-Liang Chen1, James R Fuchs3, Chenglong Li3, Pui-Kai Li3 and Jiayuh Lin1245*

Author Affiliations

1 Department of Pediatrics, The Ohio State University, Columbus, Ohio, 43210, USA

2 Molecular Cellular and Developmental Biology Program, The Ohio State University, Columbus, Ohio, 43210, USA

3 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, 43210, USA

4 Experimental Therapeutics Program, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio, 43210, USA

5 Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, College of Medicine, The Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA

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BMC Cancer 2009, 9:99  doi:10.1186/1471-2407-9-99

Published: 30 March 2009

Abstract

Background

Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer.

Methods

We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC50) were calculated using Sigma Plot 9.0 software.

Results

Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC50 values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC50 values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied.

Conclusion

The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma.