ArticleMolecular cancer therapeutics2009
Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Multi-ancestry investigation of the genomics of erectile dysfunction.Nature communications · 2025Pooled it
- ADT-030, a novel PDE10 inhibitor, demonstrates potent antitumor activity in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Sulindac as a precision microRNA modulator in early-stage K-Ras-driven oncogenesis.Cell death discovery · 2025Article
- Sulindac sulfide suppresses oncogenic transformation through let-7b-mediated repression of K-Ras signaling.Cell death discovery · 2025Article
- HDAC9 Deficiency Upregulates cGMP-dependent Kinase II to Mitigate Neuronal Apoptosis in Ischemic Stroke.Translational stroke research · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- NSAID-encapsulated nanoparticles as a targeted therapeutic platform for modulating chronic inflammation and inhibiting cancer progression: a review.Inflammopharmacology · 2025Review
- Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.Anti-cancer agents in medicinal chemistry · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- Article
- Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer.Molecules (Basel, Switzerland) · 2023Article
- Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.Frontiers in immunology · 2023Article
- Chromosome 18 Loss of Heterozygosity in Small Intestinal Neuroendocrine Tumours: Multi-Omic and Tumour Composition Analyses.Neuroendocrinology · 2023Article
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme.Pharmacological reports : PR · 2022Review
- NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase.International journal of molecular sciences · 2022Review
- Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.Frontiers in pharmacology · 2022Review
- Pros and Cons of Pharmacological Manipulation of cGMP-PDEs in the Prevention and Treatment of Breast Cancer.International journal of molecular sciences · 2021Review
- Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer.iScience · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Sulindac displays promising antineoplastic activity, but toxicities from cyclooxygenase inhibition limit its use for chemoprevention. Previous reports suggest that its anticancer properties may be attributed to a cyclooxygenase-independent mechanism, although alternative targets have not been well defined. Here, we show that sulindac sulfide (SS) induces apoptosis and inhibits the growth of human breast tumor cells with IC50 values of 60 to 85 micromol/L. Within the same concentration range, SS inhibited cyclic GMP (cGMP) hydrolysis in tumor cell lysates but did not affect cyclic AMP hydrolysis. SS did not induce apoptosis of normal human mammary epithelial cells (HMEC) nor did it inhibit phosphodiesterase (PDE) activity in HMEC lysates. SS increased intracellular cGMP levels and activated protein kinase G in breast tumor cells but not HMEC. The guanylyl cyclase (GC) activator, NOR-3, and cGMP PDE inhibitors, trequinsin and MY5445, displayed similar growth-inhibitory activity as SS, but the adenylyl cyclase activator, forskolin, and other PDE inhibitors had no effect. Moreover, GC activation increased the sensitivity of tumor cells to SS, whereas GC inhibition reduced sensitivity. By comparing PDE isozyme profiles in breast tumor cells with HMEC and determining the sensitivity of recombinant PDE isozymes to SS, PDE5 was found to be overexpressed in breast tumor cells and selectively inhibited by SS. The mechanism of SS binding to the catalytic domain of PDE5 was revealed by molecular modeling. These data suggest that PDE5 inhibition is responsible for the breast tumor cell growth-inhibitory and apoptosis-inducing activity of SS and may contribute to the chemopreventive properties of sulindac.
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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.