Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells

Carcinogenesis. 2007 Mar;28(3):713-23. doi: 10.1093/carcin/bgl189. Epub 2006 Oct 25.

Abstract

Insulin-like growth factor 1 receptor (IGF-1R) activation is required for prostate cell proliferation. Prostate cancer is one of the most commonly diagnosed malignant tumors in Western countries. Overexpression of IGF-1R in prostate cancer is associated with tumor growth. These suggest that IGF-1R inhibitory agents may be of preventive and/or therapeutic value. With evidence accumulating for a chemopreventive role of flavonoids, the effects of luteolin, a bioactive flavonoid, on IGF-1R signaling in prostate cancer cells were examined. Luteolin inhibited insulin-like growth factor 1 (IGF-1) induced activation of IGF-1R and AKT in prostate cancer PC-3 and DU145 cells. Inhibition of AKT by luteolin resulted in decreased phosphorylation of its downstream targets, including p70S6K1, GSK-3beta and FKHR/FKHRL1. Luteolin also inhibited the IGF-1-induced activation of EGFR and MAPK/ERK signaling. Luteolin inhibited expression of cyclin D1 and increased expression of p21. As a result, luteolin suppressed proliferation and induced apoptosis of prostate cancer cells. Knockdown of IGF-1R by siRNA led to inhibition of proliferation of prostate cancer cells. Results of in vivo tumor growth assay indicated that luteolin inhibited PC-3 tumor growth. Immunoblotting of the extracts of tumor tissues showed that luteolin inhibited IGF-1R/AKT signaling. Our results provide a new insight into the mechanisms that luteolin is against cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Humans
  • Luteolin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / drug effects
  • Receptor, IGF Type 1 / genetics
  • Signal Transduction / drug effects
  • Transfection

Substances

  • Anticarcinogenic Agents
  • RNA, Small Interfering
  • Cyclin D1
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • Luteolin