title: New curcumin analogues exhibit enhanced growth-suppressive activity and inhibit AKT and signal transducer and activator of transcription 3 phosphorylation in breast and prostate cancer cells.
abstract: Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development in cancer. To enhance its potency, we tested the efficacy of synthetic curcumin analogues, known as FLLL11 and FLLL12, in cancer cells. We examined the impact of FLLL11 and FLLL12 on cell viability in eight different breast and prostate cancer cell lines. FLLL11 and FLLL12 (IC(50) values 0.3-5.7 and 0.3-3.8 micromol/L, respectively) were substantially more potent than curcumin (IC(50) values between 14.4-50 micromol/L). FLLL11 and FLLL12 were also found to inhibit AKT phosphorylation and downregulate the expression of HER2/neu. In addition, we demonstrate for the first time that FLLL11 and FLLL12 inhibit phosphorylation of signal transducer and activator of transcription (STAT) 3, an oncogene frequently found to be persistently active in many cancer types. The inhibition of STAT3 signaling was confirmed by the inhibition of STAT3 DNA binding and STAT3 transcriptional activity. Furthermore, FLLL11 and FLLL12 were more effective than curcumin in inhibiting cell migration and colony formation in soft agar as well as inducing apoptosis in cancer cells. These results indicate that FLLL11 and FLLL12 exhibit more potent activities than curcumin on the inhibition of STAT3, AKT, and HER-2/neu, as well as inhibit cancer cell growth and migration, and may thus have translational potential as chemopreventive or therapeutic agents for breast and prostate cancers.
authors: Department of Pediatrics, College of Pharmacy, The Ohio State University, Columbus, OH , USA.
authors: Li
authors: L
authors: Lin
authors: Brian
authors: B
authors: Hutzen
authors: Sarah
authors: S
authors: Ball
authors: Elizabeth
authors: E
authors: Foust
authors: Matthew
authors: M
authors: Sobo
authors: Stephanie
authors: S
authors: Deangelis
authors: Bulbul
authors: B
authors: Pandit
authors: Lauren
authors: L
authors: Friedman
authors: Chenglong
authors: C
authors: Li
authors: Pui-Kai
authors: PK
authors: Li
authors: James
authors: J
authors: Fuchs
authors: Jiayuh
authors: J
authors: Lin
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C541488:FLLL-11 compound; C541487:FLLL-12 compound; D006131:Growth Inhibitors; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin