Premium
Pomegranate ellagitannin metabolite, Urolithin A, inhibits prostate cancer cell proliferation via inhibition of IGF‐1 signaling pathway
Author(s) -
Vicinanza Roberto,
Zhang Yanjun,
Henning Susanne M.,
Ma Janice,
Heber David
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.251.7
Subject(s) - protein kinase b , mapk/erk pathway , pi3k/akt/mtor pathway , cell growth , chemistry , ellagic acid , cell cycle , signal transduction , cancer research , cell , biochemistry , biology , antioxidant , polyphenol
Colonic microflora convert pomegranate ellagitannins (ETs) to ellagic acid (EA) and urolithins, primarily Urolithin A (UA). We previously demonstrated that EA and UA synergistically inhibited prostate cancer (PCa) cell growth via different mechanisms on the cell cycle. Insulin like growth factor‐1 (IGF‐1) is a potent mitogen that may activate PI3K/AKT and MAPK/ERK signaling to modulate cell cycle and proliferation. Here, we examined the effects of UA and EA on IGF‐1‐induced cell proliferation, PI3K/AKT and MAPK/ERK signaling in PCa cells. DU‐145 cells were treated for 48h with IGF‐1 (20ng/mL) with or without EA (from 3.75μM to 15μM) and UA (from 15μM to 60μM). EA and UA significantly decreased cell growth in a concentration dependent manner (p<0.001), and their combination exhibited synergism (combination index 0.378±0.043). Western blot analysis showed that EA significantly decreased basal levels of p‐ERK1/2 and p‐AKT at ser.473, while UA decreased p‐AKT at both ser.473 and thr.308. UA, but not EA, further impaired the IGF‐1‐induced AKT and ERK1/2 phosphorylation suggesting that UA inhibited cell growth by interfering with IGF‐1 signaling, providing new insights into the molecular mechanisms of ETs.