ArticleInternational journal of oncology2014
Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells.
Article in International journal of oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.Investigational new drugs · 2020Trial
- Sulforaphane Synergies with Phytochemicals and Pharmaceuticals: Implications for Healthspan.Medicines (Basel, Switzerland) · 2026Review
- Mechanisms of neuroendocrine differentiation in castration-resistant prostate cancer and advances in the treatment of neuroendocrine prostate cancer.Annals of medicine · 2025Review
- Sulforaphane's Role in Osteosarcoma Treatment: A Systematic Review and Meta-Analysis of Preclinical Studies.Biomedicines · 2025Review
- Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.International journal of molecular sciences · 2025Review
- Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance.Expert reviews in molecular medicine · 2024Review
- Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review.Cancers · 2024Review
- Modulation of Notch Signaling Pathway by Bioactive Dietary Agents.International journal of molecular sciences · 2022Review
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- Propranolol inhibits stemness of hemangioma through Jagged1.Annals of translational medicine · 2021Article
- Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies.International journal of molecular sciences · 2021Review
- The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation.Molecules (Basel, Switzerland) · 2021Article
- Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL.Pharmaceutics · 2021Review
- Cancer stem cell characteristics and their potential as therapeutic targets.Medical oncology (Northwood, London, England) · 2021Review
- Broccoli extract increases drug-mediated cytotoxicity towards cancer stem cells of head and neck squamous cell carcinoma.British journal of cancer · 2020Article
- Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway.International journal of oncology · 2020Article
- Glucosamine Enhances TRAIL-Induced Apoptosis in the Prostate Cancer Cell Line DU145.Medicines (Basel, Switzerland) · 2019Article
- Sulforaphane Induces miR135b-5p and Its Target Gene, RASAL2, thereby Inhibiting the Progression of Pancreatic Cancer.Molecular therapy oncolytics · 2019Article
- The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review.Journal of cell communication and signaling · 2018Article
- A marginal anticancer effect of regorafenib on pancreatic carcinoma cells in vitro, ex vivo, and in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.