The Phytoestrogenic Compound Cajanol from Pigeonpea Roots is Associated with the Activation of Estrogen Receptor α‐dependent Signaling Pathway in Human Prostate Cancer Cells

Abstract

In the present study, the main natural estrogen-agonist/antagonist from Pigeonpea roots was studied by the estrogen receptor α-dependent signaling pathway in human prostate cancer cell. First, the natural products with estrogenic activity in Pigeonpea roots were screened by pER8-GFP transgenic Arabidopsis, and cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) was confirmed as the active compound. Further study showed that cajanol significantly arrested the cell cycle in the G1 and G2/M phase and induced nuclei condensation, fragmentation and the formation of apoptotic bodies. Western blotting showed that cajanol modulated the ERα-dependent PI3K pathway and induced the activation of GSK3 and CyclinD1 closely following the profile of PI3K activity. Based on above results, we proposed a mechanism through which cajanol could inhibit survival and proliferation of estrogen-responsive cells (PC-3 cells) by interfering with an ERα-associated PI3K pathway, following a process that could be dependent of the nuclear functions of the ERα. Above all, we conclude that cajanol represents a valuable natural phytoestrogen source and may potentially be applicable in health food industry.