Abstract

Prostate cancer (PCa) is the second leading cause of cancer death in American population. In this manner, novel therapeutic approaches for identification of therapeutic targets for PCa has significant clinical implications. Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. To investigate the underlying mechanism by which the PCa was regulated, nanoparticles of quercetin were administrated to cells. For in vitro experiments, human PCa cell line LNCaP were involved. Cell viability assay and quantitative RT-PCR (qRT-PCR) for hedgehog signaling pathway genes were used to determine the key signaling pathway regulated for PCa progression. The cell viability gradually decreased with increased concentration of quercetin nanoparticles. At 48 h, 40 mM concentration of quercetin treatment showed near 50% of viable cells. Quercetin nanoparticles upregulates Su(Fu) mRNA expressions and downregulates gli mRNA expressions in the LNCaP cells. The results showed that the hedgehog signaling targeted inhibition may have important implications of PCa therapeutics. Additionally, the outcomes provided new mechanistic basis for further examination of quercetin nanoparticles to discover potential treatment strategies and new targets for PCa inhibition.

Highlights

  • Hedgehog (Hh) signal transduction pathway has a main role in the homeostasis, growth, survival, and malignancy [1, 2]

  • Quercetin nanoparticle preparation by microfluidic reactor High performance liquid chromatography (HPLC)-grade quercetin was purchased from Behansar Pharmaceutical Company (Iran)

  • To determine the effect of quercetin-induced cell viability, human Prostate cancer (PCa) cell line LNCaP were treated with different concentrations of quercetin

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Summary

Introduction

Hedgehog (Hh) signal transduction pathway has a main role in the homeostasis, growth, survival, and malignancy [1, 2]. The PTCH1 hedgehog receptor is a pathway target gene, which forms a negative feedback loops to maintain the pathway activity at a proper level. Hedgehog signaling activation via PTCH1 loss-of-function somatic mutations in human basal cell carcinomas (BCCs) disrupts this feedback regulation, inciting uncontrolled SMO signaling [4]. Prostate cancer (PCa) is the second leading cause of cancer death in American population In this manner, novel therapeutic approaches for identification of therapeutic targets for PCa has significant clinical implications. Cell viability assay and quantitative RT-PCR (qRT-PCR) for hedgehog signaling pathway genes were used to determine the key signaling pathway regulated for PCa progression. Conclusions: The results showed that the hedgehog signaling targeted inhibition may have important implications of PCa therapeutics. The outcomes provided new mechanistic basis for further examination of quercetin nanoparticles to discover potential treatment strategies and new targets for PCa inhibition

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