Matairesinol Targets Lipid Metabolism Reprogramming in AR-Independent Prostate Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Metabolic reprogramming, particularly lipid reprogramming, is a key driver of prostate cancer (PCa) progression.
• Lipid metabolism alterations are implicated in resistance to androgen deprivation therapy (ADT) in PCa.
• Targeting lipid reprogramming presents a potential therapeutic strategy for PCa.

Purpose of the Study:

• To investigate the therapeutic potential of Matairesinol (MA), a plant-derived lignan, in targeting lipid reprogramming in PCa cells.
• To evaluate MA's effects on PCa cell growth, apoptosis, and key genes involved in lipid metabolism.
• To identify potential molecular targets of MA using bioinformatics and molecular docking.

Main Methods:

• PC-3 cells were treated with MA, and cell viability and apoptosis were assessed.
• Quantitative PCR (qPCR) was used to evaluate the expression of genes related to fatty acid and cholesterol biosynthesis, lipid transport, and lipolysis.
• Intracellular lipid accumulation was measured using Nile red staining.
• Bioinformatics databases (DrugBank, PubChem, BindingDB) and molecular docking (AutoDock 4.2) were employed to identify MA targets.

Main Results:

• MA significantly inhibited PCa cell growth and induced apoptosis by affecting mitochondrial membrane potential.
• MA modulated the expression of genes involved in de novo fatty acid and cholesterol biosynthesis, lipid transport, and lipolysis, leading to reduced intracellular lipid accumulation.
• Bioinformatics analysis and molecular docking identified SHBG and DHRS4L2 as potential targets of MA, which was further validated by reduced mRNA levels in PC-3 cells.

Conclusions:

• MA demonstrates significant anti-cancer effects by targeting lipid metabolism in PCa cells.
• MA holds promise as a therapeutic agent for prostate cancer, particularly for ADT-resistant and metastatic castration-resistant prostate cancer (mCRPC).
• Targeting lipid reprogramming pathways with MA represents a novel therapeutic avenue for advanced prostate cancer.