ArticleOncotarget2015
Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- GANT61 surmounts drug resistance of ADR by upregulating lysosome activities and reducing BCL2 expression in HL-60/ADR cells.Cancer cell international · 2024Article
- Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo.Journal of translational medicine · 2022Article
- Article
- GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells.International journal of molecular sciences · 2020Article
- A Gli inhibitor GANT61 suppresses cell proliferation, promotes cell apoptosis and induces G1/G0 cycle retardation with a dose- and time-dependent manner through inhibiting Notch pathway in multiple myeloma.Cell cycle (Georgetown, Tex.) · 2020Article
- Article
- Hedgehog Signaling in Mesothelioma: 2019 Status.Frontiers in genetics · 2019Article
- Role of GLI Transcription Factors in Pathogenesis and Their Potential as New Therapeutic Targets.International journal of molecular sciences · 2018Review
- A novel therapeutic approach against B-cell non-Hodgkin's lymphoma through co-inhibition of Hedgehog signaling pathway and autophagy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Novel PKC-ζ to p47 phox interaction is necessary for transformation from blebbishields.Scientific reports · 2016Article
- The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.Inflammation · 2016Article
- Article
- Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation.Virology journal · 2016Article
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- Review
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe.
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