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Updated: Sep 10, 2025
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Matairesinol Targets Lipid Metabolism Reprogramming in AR-Independent Prostate Cancer Cells
Minal Mahajan1, Gauri Ghodke2, Manali Joshi2
1Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Pune-411043, Maharashtra, India.
Objective:
Metabolic reprogramming, especially lipid reprogramming, is critical in cancer progression, including prostate cancer (PCa). Androgen deprivation therapy (ADT) is commonly used to slow down tumor spread and Lipid metabolism has been linked to its resistance in PCa. This study examines the therapeutic potential of Matairesinol (MA), a plant-derived lignan, in targeting lipid reprogramming in PCa cells.
Methods:
PC-3 cells were treated with different doses of MA and its effect was studied on cell growth and induction of apoptosis by trypan blue dye exclusion and JC-1 dye assays, respectively. The altered expression of de novo fatty acid, cholesterol biosynthesis and other associated genes were evaluated by qPCR. Changes in intracellular lipid accumulation were assessed by Nile red staining. The bioinformatics approach was used to identify the main targets of MA using DrugBank, PubChem, and BindingDB databases, and molecular docking was performed with Autodock 4.2 to predict the binding of MA.
Results:
MA significantly impaired PCa cell growth and mitochondrial membrane potential, inducing apoptosis. MA modulated mRNA expression of fatty acid and cholesterol biosynthesis, lipid transport, and lipolysis-related genes, and reduced lipid accumulation. Bioinformatics analysis with DrugBank, PubChem, and BindingDB revealed the main targets of MA; and molecular docking with AutoDock 4.2 predicted MA binding and identified SHBG and DHRS4L2 as potential targets. In vitro validation confirmed that MA significantly reduced mRNA levels of SHBG and DHRS4L2 in PC-3 cell line.
Conclusion:
By targeting lipid metabolism, MA holds promising potential as a therapeutic agent for PCa, especially in ADT-resistant and Metastatic Castration Resistant Prostate Cancer (mCRPC) cases.
Insights
Matairesinol (MA) effectively targets lipid reprogramming in prostate cancer (PCa) cells, inhibiting growth and inducing apoptosis. This plant-derived lignan shows potential for treating advanced PCa, including castration-resistant forms.
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.
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