Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells

Abstract

Background: A major challenge in cancer chemotherapy has been developing safe and clinically efficacious chemotherapeutic agents. With its low toxicity profile, curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical studies have shown its inhibitory anticancer, antioxidant, anti-inflammatory, antiproliferative, and proapoptotic activities. The multiple mechanisms of the antitumor effect of curcumin putatively include down-regulating the expression of gene products such as nuclear factor-κB, growth suppression, inducing apoptosis, and modulating various signal transduction pathways and the expression of many oncogenes. The mechanisms underlying the antitumor activity of curcumin have not, however, been completely delineated. Methods: An oligonucleotide microarray chip was developed and used to profile microRNA (miRNA) expressions in pancreatic cells treated with curcumin. Transcripts with regulated expression patterns on the arrays were validated by real-time PCRs. Additionally, potential mRNA targets were analyzed bioinformatically and confirmed with flow cytometry experiments. Results: Curcumin alters miRNA expression in human pancreatic cells, up-regulating miRNA-22 and down-regulating miRNA-199a*, as confirmed by TaqMan real-time PCR. Upregulation of miRNA-22 expression by curcumin or by transfection with miRNA-22 mimetics in the PxBC-3 pancreatic cancer cell line suppressed expression of its target genes SP1 transcription factor (SP1) and estrogen receptor 1 (ESR1), while inhibiting miRNA-22 with antisense enhanced SP1 and ESR1 expression. Conclusions: These observations suggest that modulation of miRNA expression may be an important mechanism underlying the biological effects of curcumin. Copyright © 2008 American Association for Cancer Research.