title: New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells.
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 microM and 13.31 microM. 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 microM and 4.48 microM. 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 microM. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, The Ohio State University, Columbus, Ohio, 43210, USA. cen.ling@mayo.edu
authors.forename: Ling
authors.initials: L
authors.lastname: Cen
authors.forename: Brian
authors.initials: B
authors.lastname: Hutzen
authors.forename: Sarah
authors.initials: S
authors.lastname: Ball
authors.forename: Stephanie
authors.initials: S
authors.lastname: DeAngelis
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: James R
authors.initials: JR
authors.lastname: Fuchs
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin