ArticleScientific reports2022
Anti-neoplastic action of Cimetidine/Vitamin C on histamine and the PI3K/AKT/mTOR pathway in Ehrlich breast cancer.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy.Archives of pharmacal research · 2026Review
- Ozonated Water Modulates Cell Proliferation and Vascular Density in Solid Ehrlich Tumor of Mice.Cancers · 2026Article
- Nutritional Impact on Breast Cancer in Menopausal and Post-Menopausal Patients Treated with Aromatase Inhibitors.Cancers · 2025Review
- Innovative horizons: harnessing drug repositioning for targeted therapeutics in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Isogarcinol Reduces MARS Levels and Deactivates the PI3K/AKT Pathway to Suppress the Malignant Properties of Breast Cancer Cells.Cell biochemistry and biophysics · 2025Article
- Machine learning model reveals the risk, prognosis, and drug response of histamine-related signatures in pancreatic cancer.Discover oncology · 2025Article
- High-dose Ascorbate Exhibits Anti-proliferative and Anti-invasive Effects Dependent on PTEN/AKT/mTOR Pathway in Endometrial CancerInternational journal of biological sciences · 2025Article
- Article
- Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma.Biomolecules & biomedicine · 2024Article
- Pathophysiological role of histamine signaling and its implications in glioblastoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2024Review
- A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer:International journal of pharmaceutics: X · 2024Article
- The Involvement of Ascorbic Acid in Cancer Treatment.Molecules (Basel, Switzerland) · 2024Review
- Sphingomyelin Metabolism Modifies Luminal A Breast Cancer Cell Line under a High Dose of Vitamin C.International journal of molecular sciences · 2023Article
- Effects of Echinacoside on Ehrlich Carcinoma in Rats by Targeting Proliferation, Hypoxia and Inflammation.Cureus · 2023Article
- Review
- Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment.Medical oncology (Northwood, London, England) · 2023Review
- Risk stratification based on DNA damage-repair-related signature reflects the microenvironmental feature, metabolic status and therapeutic response of breast cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main focus of our study is to assess the anti-cancer activity of cimetidine and vitamin C via combating the tumor supportive role of mast cell mediators (histamine, VEGF, and TNF-α) within the tumor microenvironment and their effect on the protein kinase A(PKA)/insulin receptor substrate-1(IRS-1)/phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase-1 (AKT)/mammalian target of rapamycin (mTOR) cue in Ehrlich induced breast cancer in mice. In vitro study was carried out to evaluate the anti-proliferative activity and combination index (CI) of the combined drugs. Moreover, the Ehrlich model was induced in mice via subcutaneous injection of Ehrlich ascites carcinoma cells (EAC) in the mammary fat pad, and then they were left for 9 days to develop obvious solid breast tumor. The combination therapy possessed the best anti-proliferative effect, and a CI < 1 in the MCF7 cell line indicates a synergistic type of drug interaction. Regarding the in vivo study, the combination abated the elevation in the tumor volume, and serum tumor marker carcinoembryonic antigen (CEA) level. The serum vascular endothelial growth factor (VEGF) level and immunohistochemical staining for CD34 as markers of angiogenesis were mitigated. Additionally, it reverted the state of oxidative stress and inflammation. Meanwhile, it caused an increment in apoptosis, which prevents tumor survival. Furthermore, it tackled the elevated histamine and cyclic adenosine monophosphate (cAMP) levels, preventing the activation of the (PKA/IRS-1/PI3K/AKT/mTOR) cue. Finally, we concluded that the synergistic combination provided a promising anti-neoplastic effect via reducing the angiogenesis, oxidative stress, increasing apoptosis,as well as inhibiting the activation of PI3K/AKT/mTOR cue, and suggesting its use as a treatment option for breast cancer.
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