ArticleBMC cancer2013
Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
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- Mechanisms of pulmonary vascular dysfunction in pulmonary hypertension and implications for novel therapies.American journal of physiology. Heart and circulatory physiology · 2022Review
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- Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors.International journal of molecular sciences · 2021Review
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- Efficacy of a Three Drug-Based Therapy for Neuroblastoma in Mice.International journal of molecular sciences · 2021Article
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- Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy.ChemMedChem · 2020Review
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- Carbonic Anhydrase Inhibition Ameliorates Inflammation and Experimental Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2019Article
- Human bronchial carcinoid tumor initiating cells are targeted by the combination of acetazolamide and sulforaphane.BMC cancer · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBronchial carcinoids are pulmonary neuroendocrine cell-derived tumors comprising typical (TC) and atypical (AC) malignant phenotypes. The 5-year survival rate in metastatic carcinoid, despite multiple current therapies, is 14-25%. Hence, we are testing novel therapies that can affect the proliferation and survival of bronchial carcinoids.
methodsIn vitro studies were used for the dose-response (AlamarBlue) effects of acetazolamide (AZ) and sulforaphane (SFN) on clonogenicity, serotonin-induced growth effect and serotonin content (LC-MS) on H-727 (TC) and H-720 (AC) bronchial carcinoid cell lines and their derived NOD/SCID mice subcutaneous xenografts. Tumor ultra structure was studied by electron microscopy. Invasive fraction of the tumors was determined by matrigel invasion assay. Immunohistochemistry was conducted to study the effect of treatment(s) on proliferation (Ki67, phospho histone-H3) and neuroendocrine phenotype (chromogranin-A, tryptophan hydroxylase).
resultsBoth compounds significantly reduced cell viability and colony formation in a dose-dependent manner (0-80 μM, 48 hours and 7 days) in H-727 and H-720 cell lines. Treatment of H-727 and H-720 subcutaneous xenografts in NOD/SCID mice with the combination of AZ + SFN for two weeks demonstrated highly significant growth inhibition and reduction of 5-HT content and reduced the invasive capacity of H-727 tumor cells. In terms of the tumor ultra structure, a marked reduction in secretory vesicles correlated with the decrease in 5-HT content.
conclusionsThe combination of AZ and SFN was more effective than either single agent. Since the effective doses are well within clinical range and bioavailability, our results suggest a potential new therapeutic strategy for the treatment of bronchial carcinoids.
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