ArticleCancer cell international2024
Integrated proteomics and metabolomics analyses reveal new insights into the antitumor effects of valproic acid plus simvastatin combination in a prostate cancer xenograft model associated with downmodulation of YAP/TAZ signaling.
Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Phase Separation of NFIB Suppresses SLC3A2-Mediated Ferroptosis in Castration-Resistant Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual inhibition of mTOR and HSP90 enhances cisplatin efficacy and overcomes resistance in ovarian cancer.Cell death & disease · 2026Article
- Valproic acid improves the efficacy of oxaliplatin/fluoropyrimidine-based chemotherapy by targeting cancer stem cell via β-Catenin modulation in colorectal cancer.Cell death & disease · 2025Article
- Metabolomic and Proteomic Analyses Unveil That Polyethylene Glycol-Polycaprolactone-Loaded Curcumin Nanoparticles Induce Mitochondrial Dysfunction and Metabolic Reprogramming to Suppress Melanoma Growth.ACS applied materials & interfaces · 2025Article
- Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy.Journal of clinical medicine · 2025Review
- Role ofMicroorganisms · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundDespite advancements in therapeutic approaches, including taxane-based chemotherapy and androgen receptor-targeting agents, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable tumor, highlighting the need for novel strategies that can target the complexities of this disease and bypass the development of drug resistance mechanisms. We previously demonstrated the synergistic antitumor interaction of valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitory activity, with the lipid-lowering drug simvastatin (SIM). This combination sensitizes mCRPC cells to docetaxel treatment both in vitro and in vivo by targeting the cancer stem cell compartment via mevalonate pathway/YAP axis modulation.
methodsHere, using a combined proteomic and metabolomic/lipidomic approach, we characterized tumor samples derived from 22Rv1 mCRPC cell-xenografted mice treated with or without VPA/SIM and performed an in-depth bioinformatics analysis.
resultsWe confirmed the specific impact of VPA/SIM on the Hippo-YAP signaling pathway, which is functionally related to the modulation of cancer-related extracellular matrix biology and metabolic reprogramming, providing further insights into the molecular mechanism of the antitumor effects of VPA/SIM.
conclusionsIn this study, we present an in-depth exploration of the potential to repurpose two generic, safe drugs for mCRPC treatment, valproic acid (VPA) and simvastatin (SIM), which already show antitumor efficacy in combination, primarily affecting the cancer stem cell compartment via MVP/YAP axis modulation. Bioinformatics analysis of the LC‒MS/MS and
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