ArticleCancer prevention research (Philadelphia, Pa.)2013
Chemoprevention of colon and small intestinal tumorigenesis in APC(min/+) mice by SHetA2 (NSC721689) without toxicity.
Article in Cancer prevention research (Philadelphia, Pa.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 32 citations in OpenAlex.
- Mortalin and PINK1/Parkin-Mediated Mitophagy Represent Ovarian Cancer-Selective Targets for Drug Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prevention of hypertension-induced renal vascular dysfunction through a p66Shc-targeted mechanism.American journal of physiology. Renal physiology · 2025Article
- Targeting HSP70-E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer.Journal of medical virology · 2024Article
- Manipulation of metabolic responses enhances SHetA2 efficacy without toxicity in cervical cancer cell lines and xenografts.Gynecologic oncology · 2024Article
- Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing.The AAPS journal · 2023Article
- SHetA2 Attack on Mortalin and Colleagues in Cancer Therapy and Prevention.Frontiers in cell and developmental biology · 2022Review
- Distinct mechanism of cervical cancer cell death caused by the investigational new drug SHetA2.Frontiers in oncology · 2022Article
- Abrogating the Interaction Between p53 and Mortalin (Grp75/HSPA9/mtHsp70) for Cancer Therapy: The Story so far.Frontiers in cell and developmental biology · 2022Review
- Article
- Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53.International journal of cancer · 2020Article
- Vaginal Suppositories Containing SHetA2 to Treat Cervical Dysplasia: Pharmacokinetics of Daily Doses and Preliminary Safety Profile.Journal of pharmaceutical sciences · 2020Article
- Article
- Physiologically Based Pharmacokinetic Modeling and Tissue Distribution Characteristics of SHetA2 in Tumor-Bearing Mice.The AAPS journal · 2020Article
- Development and validation of a reverse phase HPLC method for SHetA2, a novel anti-cancer drug, in mouse biological samples.Journal of pharmaceutical and biomedical analysis · 2019Article
- The application of ApcJournal of cancer research and clinical oncology · 2019Review
- Pharmacokinetics and Pharmacodynamics of Escalating Doses of SHetA2 After Vaginal Administration to Mice.Journal of pharmaceutical sciences · 2018Article
- Influence of the estrus cycle of the mouse on the disposition of SHetA2 after vaginal administration.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2018Article
- Development of a dietary formulation of the SHetA2 chemoprevention drug for mice.Investigational new drugs · 2018Article
- Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma.Molecular medicine reports · 2018Article
- Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia.Journal of pharmaceutical sciences · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The occurrence of intestinal polyps in people at high risk for developing colorectal cancer provides an opportunity to test the efficacy of chemoprevention agents. In this situation of treating otherwise healthy people, the potential for toxicity must be minimal. The small-molecule flexible heteroarotinoid (Flex-Het), called SHetA2, has chemoprevention activity in organotypic cultures in vitro and lack of toxicity at doses capable of inhibiting xenograft tumor growth in vivo. The objective of this study was to evaluate SHetA2 chemoprevention activity and toxicity in the APC(min/+) murine model. Oral administration of SHetA2 at 30 and 60 mg/kg five days per week for 12 weeks significantly reduced development of intestinal polyps by 40% to 60% depending on the dose and sex of the treatment group. Immunohistochemical and Western blot analysis of polyps showed reduced levels of cyclin D1 and proliferating cell nuclear antigen in both SHetA2 treatment groups. Western blot analysis also showed SHetA2 induction of E-cadherin, Bax, and caspase-3 cleavage along with reduction in Bcl-2, COX-2, and VEGF, consistent with SHetA2 regulation of apoptosis, inflammation, and angiogenesis. Neither dose caused weight loss nor gross toxicity in APC(min/+) or wild-type littermates. Magnetic resonance imaging (MRI) of cardiac function showed no evidence of SHetA2 toxicity. SHetA2 did not alter left ventricular wall thickness. In summary, SHetA2 exerts chemoprevention activity without overt or cardiac toxicity in the APC(min/+) model. SHetA2 modulation of biomarkers in colon polyps identifies potential pharmacodynamic endpoints for SHetA2 clinical trials.
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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.