ArticleCarcinogenesis2010
Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.
Article in Carcinogenesis, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Phospho-NSAIDs have enhanced efficacy in mice lacking plasma carboxylesterase: implications for their clinical pharmacology.Pharmaceutical research · 2015Article
- The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent.Biochemical pharmacology · 2014Article
- Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate.International journal of oncology · 2014Article
- Aerosol administration of phospho-sulindac inhibits lung tumorigenesis.Molecular cancer therapeutics · 2013Article
- Topically applied phospho-sulindac hydrogel is efficacious and safe in the treatment of experimental arthritis in rats.Pharmaceutical research · 2013Article
- The anticancer effect of phospho-tyrosol-indomethacin (MPI-621), a novel phosphoderivative of indomethacin: in vitro and in vivo studies.Carcinogenesis · 2013Article
- Polyamines and cancer: implications for chemotherapy and chemoprevention.Expert reviews in molecular medicine · 2013Review
- New NSAID targets and derivatives for colorectal cancer chemoprevention.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2013Review
- The proapoptotic effect of traditional and novel nonsteroidal anti-inflammatory drugs in mammalian and yeast cells.Oxidative medicine and cellular longevity · 2013Review
- Prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs), more than meets the eye: a critical review.International journal of molecular sciences · 2012Review
- Phospho-sulindac (OXT-328) inhibits the growth of human lung cancer xenografts in mice: enhanced efficacy and mitochondria targeting by its formulation in solid lipid nanoparticles.Pharmaceutical research · 2012Article
- Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer.International journal of oncology · 2012Article
- Regioselective oxidation of phospho-NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety.British journal of pharmacology · 2012Article
- Sterically stabilized liposomes incorporating the novel anticancer agent phospho-ibuprofen (MDC-917): preparation, characterization, and in vitro/in vivo evaluation.Pharmaceutical research · 2012Article
- Phospho-ibuprofen (MDC-917) incorporated in nanocarriers: anti-cancer activity in vitro and in vivo.British journal of pharmacology · 2012Article
- The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect of difluoromethylornithine.British journal of pharmacology · 2012Article
- Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity.The Journal of pharmacology and experimental therapeutics · 2012Article
- Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing.Breast cancer (Dove Medical Press) · 2012Article
- Oxidative stress mediates through apoptosis the anticancer effect of phospho-nonsteroidal anti-inflammatory drugs: implications for the role of oxidative stress in the action of anticancer agents.The Journal of pharmacology and experimental therapeutics · 2011Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy. Here, we evaluated the effect of a new sulindac derivative, phospho-sulindac or OXT-922, on the growth of human cancer cell lines and its mechanism of action. OXT-922 inhibited the growth of human cancer cell lines originating from colon, pancreas and breast ~11- to 30-fold more potently than sulindac. This effect was mediated by a strong cytokinetic effect. Compared with control, OXT-922 inhibited cell proliferation by up to 67%, induced apoptosis 4.1-fold over control and blocked the G(1) to S cell cycle phase transition. OXT-922 suppressed the levels of cell cycle regulating proteins, including cyclins D(1) and D(3) and Cyclin-dependent kinases (CDK) 4 and 6. The levels of intracellular reactive oxygen species (ROS), especially those of mitochondrial O₂ⁱ⁻, were markedly elevated (5.5-fold) in response to OXT-922. ROS collapsed the mitochondrial membrane potential and triggered apoptosis, which was largely abrogated by antioxidants. OXT-922 suppressed nuclear factor-kappaB activation and downregulated thioredoxin-1 expression. It also suppressed the production of prostaglandin E(2) and decreased cyclooxygenase-1 expression. Similar to sulindac, OXT-922 enhanced spermidine/spermine N(1)-acetyltransferase activity, reduced the cellular polyamine content and synergized with difluoromethylornithine to inhibit cancer cell proliferation and induce apoptosis. Our results suggest that OXT-922 possesses promising anticancer properties and deserves further evaluation.
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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.