Introduction:
The sex-steroids, dihydrotestosterone (DHT) and estradiol (E2) have a crucial role in the maintenance of normal health of the prostate gland. The profile of these hormones alters with advancing age, causing dysregulation of stromal-epithelial interactions. This phenomenon has been linked to the emergence of prostate pathologies (benign prostate hyperplasia and prostate cancer) in aged men.
In recent times, phytonutrients have received considerable attention in treatment of various disorders, including cancers. Quercetin is a powerful anti-oxidant, belonging to the flavonoid family and is epidemiologically associated with decreased incidence of prostate pathologies in Asian countries. Further, substantial evidence from literature indicating anti-proliferative effects of flavonoids on cancerous cell lines prompted us to evaluate the impact of quercetin on hormone-mediated stromal epithelial interactions in normal prostate cells.
Aim and Objectives:
The aim of the study was to explore the role of quercetin on hormone mediated stromal-epithelial interaction in prostate cells with the following objectives:
1. To check the effect of quercetin on the viability/proliferation of normal prostate epithelial cells (growing under the influence of stromal cell secretome).
2. To check if quercetin treatment can suppress the stromal cells’ proliferation and/or the release of growth promoting factors (that induce aberrant proliferation of epithelial cells) from stromal cells.
Material and Methods:
Non-neoplastic prostate stromal (WPMY-1) and epithelial (RWPE-1) cells were used as model cell lines. E2 (20 pM) and DHT (10 nM) were used to mimic the environment of aged prostate in vitro. To explore the intricate relationship between stroma and epithelium, a one-way paracrine contact was created between the two cell lines by using conditioned medium (CM) from stromal cells on epithelial cells.
Result:
Conditioned medium collected from WPMY-1 cells significantly increased the proliferation of RWPE-1 cells as compared to control. Quercetin significantly downregulated the aberrant epithelial proliferation, caused by stromal CM. Further, stromal cells’ proliferation was inhibited by quecertin treatment. 3-D cell culture observation revealed decreased spheroid size, branching pattern, and number of live cells after quercetin treatment.
Conclusion:
Our findings suggest that quercetin helps to regulate aberrant epithelial and stromal proliferation. Further, it modulates the stromal secretome's proliferative potential.