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

Jing Fang, Qiong Zhou, Xiang Lin Shi, Bing Hua Jiang

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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-3β 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.

Original languageEnglish
Pages (from-to)713-723
Number of pages11
Issue number3
StatePublished - Mar 2007

Bibliographical note

Funding Information:
This work was supported by grants from Science and Technology Commission of Shanghai Municipality (No. 05DJ14009 and 04DZ14007) and a grant from National Natural Science Foundation of China (No. 30470361 and 30570962).

ASJC Scopus subject areas

  • Cancer Research


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