Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells.
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.
Fang
Jing
J
The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy of Sciences, Shanghai 200031, China. jfang@sibs.ac.cn
Zhou
Qiong
Q
Shi
Xiang-lin
XL
Jiang
Bing-hua
BH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D016588:Anticarcinogenic Agents; D034741:RNA, Small Interfering; D019938:Cyclin D1; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D047311:Luteolin