ArticleScientific reports2019
Cyclopamine tartrate, a modulator of hedgehog signaling and mitochondrial respiration, effectively arrests lung tumor growth and progression.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 24 citations in OpenAlex.
- Endogenous Ligands of TLR4 in Microglia: Potential Targets for Related Neurological Diseases.Current drug targets · 2024Review
- Identifying prognostic genes related PANoptosis in lung adenocarcinoma and developing prediction model based on bioinformatics analysis.Scientific reports · 2023Article
- Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions.International journal of molecular sciences · 2023Review
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- EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.BMC bioinformatics · 2023Article
- Comprehensive analysis reveals the potential value of inflammatory response genes in the prognosis, immunity, and drug sensitivity of lung adenocarcinoma.BMC medical genomics · 2022Article
- Modulation of heme and tumor vascular oxygenation- a novel strategy for lung cancer therapy.Oncoscience · 2022Article
- The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy.Frontiers in oncology · 2022Review
- Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha.International journal of molecular sciences · 2021Review
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Oxygen-Enhanced Optoacoustic Tomography Reveals the Effectiveness of Targeting Heme and Oxidative Phosphorylation at Normalizing Tumor Vascular Oxygenation.Cancer research · 2020Article
- Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.International journal of molecular sciences · 2020Review
- Article
- Mitochondria Targeting as an Effective Strategy for Cancer Therapy.International journal of molecular sciences · 2020Review
- Detecting Cancer Survival Related Gene Markers Based on Rectified Factor Network.Frontiers in bioengineering and biotechnology · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer remains the leading cause of cancer-related death, despite the advent of targeted therapies and immunotherapies. Therefore, it is crucial to identify novel molecular features unique to lung tumors. Here, we show that cyclopamine tartrate (CycT) strongly suppresses the growth of subcutaneously implanted non-small cell lung cancer (NSCLC) xenografts and nearly eradicated orthotopically implanted NSCLC xenografts. CycT reduces heme synthesis and degradation in NSCLC cells and suppresses oxygen consumption in purified mitochondria. In orthotopic tumors, CycT decreases the levels of proteins and enzymes crucial for heme synthesis, uptake, and oxidative phosphorylation (OXPHOS). CycT also decreases the levels of two regulators promoting OXPHOS, MYC and MCL1, and effectively alleviates tumor hypoxia. Evidently, CycT acts via multiple modes to suppress OXPHOS. One mode is to directly inhibit mitochondrial respiration/OXPHOS. Another mode is to inhibit heme synthesis and degradation. Both modes appear to be independent of hedgehog signaling. Addition of heme to NSCLC cells partially reverses the effect of CycT on oxygen consumption, proliferation, and tumorigenic functions. Together, our results strongly suggest that CycT suppress tumor growth in the lung by inhibiting heme metabolism and OXPHOS. Targeting heme metabolism and OXPHOS may be an effective strategy to combat lung cancer.
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