Guggulsterone Enhances NKX3.1 Expression and Induces Apoptosis in Prostate Cancer Cells: Implications for Chemoprevention

Abstract

AbstractAimProstate cancer is a leading cause of cancer-related mortality, necessitating novel therapeutic and preventive strategies. This study aimed to investigate the anti-cancer properties of Guggulsterone (GS) on prostate cancer cells, specifically focusing on its effects on homeobox protein NKX3.1, apoptosis, and mitochondrial function.MethodThe study utilized the LNCaP prostate cancer cell line and involved cell culture, dose-response analysis, flow cytometry for apoptosis quantification, siRNA-mediated knockdown of NKX3.1, mitochondrial membrane potential assessment using TMRM staining, qRT-PCR analysis, and Western blotting. The stability of NKX3.1 mRNA and protein in response to GS was also evaluated.ResultGS treatment induced apoptosis in LNCaP cells in a dose and time-dependent manner, with an impact on early and late-stage apoptosis. This effect was mediated, at least in part, through the upregulation of NKX3.1. GS enhanced NKX3.1 expression at both the protein and mRNA levels, even in the absence of androgens. Furthermore, GS treatment extended the half-life of NKX3.1 mRNA and protein, suggesting an effect on their stability.ConclusionThis study provides valuable insights into the anti-cancer mechanisms of GS in prostate cancer cells. The upregulation of NKX3.1 by GS and its role in mediating apoptosis offers NKX3.1 as a potential prevention target for PCa. The findings open new research avenues for the development of targeted therapies that stabilize NKX3.1 expression and protect mitochondrial function. Further investigations are needed to understand the intricate molecular mechanisms underlying GS’s effects fully, potentially improving prostate cancer management and outcomes.