Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells

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 FILM 1 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 (IC50 values between 0.28-3.2 and 0.91-3.43 mu mol/l, respectively) were substantially more potent than curcumin (IC50 values between 8.67 and 20.35 mu mol/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. Anti-Cancer Drugs 20:444-449 (C) 2009 Wolters Kluwer Health I Lippincott Williams & Wilkins.