title: Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells.
abstract: Curcumin, a yellow pigment and the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development in several types of cancer. However, its low bioavailability and potency prevent it from being effective in most chemotherapeutic applications. One potential means of circumventing this problem has been the creation of synthetic curcumin analogues. We tested the efficacy of two such analogues, known as FLLL11 and FLLL12, in human pancreatic cancer cell lines. We compared the impact of curcumin with FLLL11 and FLLL12 on cell viability in five different pancreatic cancer cell lines. Although all three compounds were capable of lowering viability in all cell lines tested, FLLL11 and FLLL12 (IC(50) values between 0.28-3.2 and 0.91-3.43 micromol/l, respectively) were substantially more potent than curcumin (IC(50) values between 8.67 and 20.35 micromol/l). In addition, FLLL11 and FLLL12 inhibited phosphorylation of signal transducer and activator of transcription 3 and AKT, two cell signaling pathways frequently found persistently active in many forms of cancer. Furthermore, FLLL11 and FLLL12 were found to be more effective than curcumin in inducing apoptosis as evidenced by increased cleavage of PARP and caspase-3 in pancreatic cancer cell lines. These results indicate that the curcumin analogues, FLLL11 and FLLL12, are more effective than curcumin in inhibiting cell viability and inducing apoptosis, and may have translational potential as chemopreventive or therapeutic agents for pancreatic cancer.
authors.affiliation: Department of Pediatrics, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43205, USA
authors.forename: Lauren
authors.initials: L
authors.lastname: Friedman
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Sarah
authors.initials: S
authors.lastname: Ball
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: James
authors.initials: J
authors.lastname: Fuchs
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; C541488:FLLL-11 compound; C541487:FLLL-12 compound; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin