ArticlePloS one2013
Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 77 citations in OpenAlex.
- Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition.International journal of molecular sciences · 2024Article
- Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition.Nucleic acids research · 2024Article
- Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.Journal of cancer research and clinical oncology · 2023Review
- Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis.Arthritis research & therapy · 2023Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Aa-Z2 triggers ROS-induced apoptosis of osteosarcoma by targeting PDK-1.Journal of translational medicine · 2023Article
- Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling.Biomedicines · 2022Article
- Signaling pathways in the regulation of cancer stem cells and associated targeted therapy.MedComm · 2022Review
- Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer.Cell death & disease · 2022Article
- Arsenic compound sensitizes homologous recombination proficient ovarian cancer to PARP inhibitors.Cell death discovery · 2021Article
- Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.Psychopharmacology · 2021Article
- Arsenic trioxide and curcumin attenuate cisplatin-induced renal fibrosis in rats through targeting Hedgehog signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Review
- The Role of Hedgehog Pathway in Female Cancers.Journal of cancer science and clinical therapeutics · 2020Article
- Evaluation of canonical Hedgehog signaling pathway inhibition in canine osteosarcoma.PloS one · 2020Article
- TGF-β Promotes the Proliferation of Microglia In Vitro.Brain sciences · 2019Article
- Melarsomine suppresses canine osteosarcoma cell survival via inhibition of Hedgehog-GLI signaling.The Journal of veterinary medical science · 2019Article
- Beyond Cisplatin: Combination Therapy with Arsenic Trioxide.Inorganica chimica acta · 2019Article
- Article
- Tranilast enhances the effect of anticancer agents in osteosarcoma.Oncology reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog pathway is activated in various types of malignancies. We previously reported that inhibition of SMO or GLI prevents osteosarcoma growth in vitro and in vivo. Recently, it has been reported that arsenic trioxide (ATO) inhibits cancer growth by blocking GLI transcription. In this study, we analyzed the function of ATO in the pathogenesis of osteosarcoma. Real-time PCR showed that ATO decreased the expression of Hedgehog target genes, including PTCH1, GLI1, and GLI2, in human osteosarcoma cell lines. WST-1 assay and colony formation assay revealed that ATO prevented osteosarcoma growth. These findings show that ATO prevents GLI transcription and osteosarcoma growth in vitro. Flow cytometric analysis showed that ATO promoted apoptotic cell death. Comet assay showed that ATO treatment increased accumulation of DNA damage. Western blot analysis showed that ATO treatment increased the expression of γH2AX, cleaved PARP, and cleaved caspase-3. In addition, ATO treatment decreased the expression of Bcl-2 and Bcl-xL. These findings suggest that ATO treatment promoted apoptotic cell death caused by accumulation of DNA damage. In contrast, Sonic Hedgehog treatment decreased the expression of γH2AX induced by cisplatin treatment. ATO re-induced the accumulation of DNA damage attenuated by Sonic Hedgehog treatment. These findings suggest that ATO inhibits the activation of Hedgehog signaling and promotes apoptotic cell death in osteosarcoma cells by accumulation of DNA damage. Finally, examination of mouse xenograft models showed that ATO administration prevented the growth of osteosarcoma in nude mice. Because ATO is an FDA-approved drug for treatment of leukemia, our findings suggest that ATO is a new therapeutic option for treatment of patients with osteosarcoma.
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