Enterolactone inhibits insulin-like growth factor-1 receptor signaling in human prostatic carcinoma PC-3 cells.

Academic Article

Abstract

  • Enterolactone, a major metabolite of plant-based lignans, has been shown to inhibit prostate cancer growth and development, but the mechanistic basis for its anticancer activity remains largely unknown. Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) signaling is critical for prostate cancer cell growth and progression. This study examined whether the growth inhibitory effect of enterolactone was related to changes in the IGF-1/IGF-1R system in PC-3 prostate cancer cells. At nutritionally relevant concentrations (20-60 micromol/L), enterolactone inhibited IGF-1-induced activation of IGF-1R and its downstream AKT and mitogen-activated protein kinase/extracellular-signal regulated kinase signaling pathways. Inhibition of AKT by enterolactone resulted in decreased phosphorylation of its downstream targets, including p70S6K1 and glycogen synthase kinase-3 beta. Enterolactone also inhibited cyclin D1 expression. As a result, enterolactone inhibited proliferation and migration of PC-3 cells. Knockdown of IGF-1R by plasmids with siRNA (si) against IGF-1R mRNA resulted in inhibition of proliferation of PC-3 cells and cell numbers did not differ when the si-IGF-1R groups (cells transfected with plasmids containing siRNA against IGF-1R mRNA) were treated or untreated with enterolactone. These results suggest that enterolactone suppresses proliferation and migration of prostate cancer cells, at least partially, through inhibition of IGF-1/IGF-1R signaling. The finding of this study provides new insights into the molecular mechanisms that enterolactone exerts against prostate cancer.
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    Keywords

  • 4-Butyrolactone, Cell Line, Tumor, Cell Movement, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Insulin-Like Growth Factor I, Lignans, Male, Phosphotyrosine, Prostatic Neoplasms, Proto-Oncogene Proteins c-akt, Receptor, IGF Type 1, Signal Transduction
  • Digital Object Identifier (doi)

    Author List

  • Chen L-H; Fang J; Sun Z; Li H; Wu Y; Demark-Wahnefried W; Lin X
  • Start Page

  • 653
  • End Page

  • 659
  • Volume

  • 139
  • Issue

  • 4