ArticleJournal of experimental & clinical cancer research : CR2015
Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ.Journal of translational medicine · 2025Article
- Inhibition of anti-apoptotic Bcl-2 family members promotes synergistic cell death with ER stress inducers by disrupting autophagy in glioblastoma.Cell death discovery · 2025Article
- Uncovering the connection between obesity and thyroid cancer: the therapeutic potential of adiponectin receptor agonist in the AdipoR2-ULK axis.Cell death & disease · 2024Article
- The new insights into autophagy in thyroid cancer progression.Journal of translational medicine · 2023Review
- The pan-Bcl-2 inhibitor obatoclax promotes differentiation and apoptosis of acute myeloid leukemia cells.Investigational new drugs · 2020Article
- Allicin activates autophagic cell death to alleviate the malignant development of thyroid cancer.Experimental and therapeutic medicine · 2018Article
- The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in vitro and in vivo.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis.Oncotarget · 2016Article
- The BH3 mimetic drug ABT-737 induces apoptosis and acts synergistically with chemotherapeutic drugs in thyroid carcinoma cells.Cancer cell international · 2016Article
- Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe evasion of cell death is one of the hallmarks of cancer, contributing to both tumor progression and resistance to therapy. Dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to conventional anticancer treatments and patients with these tumors are difficult to treat. BH3 mimetics are a new class of drugs that target anti-apoptotic proteins of the BCL-2 family and promote cell death. The purpose of this study was to analyze the molecular effects of the BH3 mimetic GX15-070 on thyroid carcinoma cell lines and to characterize cell death induced by GX15-070.
methodsA total of 17 cell lines derived from follicular, papillary, and anaplastic thyroid carcinomas were treated with GX15-070. Cell viability was measured with MTT assay while cell cycle phase distribution and subG1 peaks were determined after propidium iodide staining. We assessed cell death via the caspase 3/7 activity, caspase cleavage products, lactate dehydrogenase (LDH) liberation assays, and a LC3 analysis by western blot. Ultrastructural changes were analysed by electron microscopy of GX15-070-treated cells.
resultsAfter GX15-070 treatment, the number of viable cells was decreased in all cell lines examined, with IC50 values ranging from 48nM to 3.25 μM. We observed biochemical markers of autophagic cell death and necrosis like LC3 conversion and LDH release after the GX15-070 treatment. Electron microscopy revealed several common characteristic ultrastructural changes like swelling of mitochondria, dilatation of rough endoplasmic reticulum, membrane blebbing and formation of vacuoles. GX15-070 treatment induced DNA fragmentation detected by subG1-peak induction and an arrest in G1 phase of the cell cycle. Caspase activation after GX15-070 incubation was detected but had no effect on viability of cells.
conclusionsWith these experiments we demonstrated the efficacy of the BH3 mimetic drug GX15-070 acting against dedifferentiated thyroid carcinoma cells of various histological origins by the induction of cell death. GX15-070-treated cells underwent non-classical cell death with signs of apoptosis, autophagy and necrosis in parallel. GX15-07 and related compounds thus may be a new therapeutic option for dedifferentiated thyroid carcinoma of various histological subtypes.
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