ArticlePloS one2013
RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- CDKL3 promotes osteosarcoma progression by activating Akt/PKB.Life science alliance · 2020Article
- Autophagy Regulation by the Translation Machinery and Its Implications in Cancer.Frontiers in oncology · 2020Review
- The relationship between autophagy and the immune system and its applications for tumor immunotherapy.Molecular cancer · 2019Review
- Article
- Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells.Journal of experimental & clinical cancer research : CR · 2018Article
- Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines.Drug design, development and therapy · 2018Article
- New Insights into the Role of Autophagy in Tumor Immune Microenvironment.International journal of molecular sciences · 2017Review
- Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment.Oncotarget · 2016Review
- The estrogen metabolite 2-methoxyestradiol regulates eukaryotic initiation factor 4E (eIF4E) and inhibits protein synthesis in MG63 osteosarcoma cells.Genes & diseases · 2016Article
- Atg7 in development and disease: panacea or Pandora's Box?Protein & cell · 2015Review
- 2-methoxyestradiol and disorders of female reproductive tissues.Hormones & cancer · 2014Review
- Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles.International journal of nanomedicine · 2014Article
- Involvement of interleukin-1β in the autophagic process of microglia: relevance to Alzheimer's disease.Journal of neuroinflammation · 2013Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Surgical resection and adjunctive chemotherapy are the only widely available options of treatment for this disease. Anti-tumor compound 2-Methoxyestradiol (2-ME) triggers cell death through the induction of apoptosis in osteosarcoma cells, but not in normal osteoblasts. In this report, we have investigated whether autophagy plays a role in 2-ME actions on osteosarcoma cells. Transmission electron microscopy imaging shows that 2-ME treatment leads to the accumulation of autophagosomes in human osteosarcoma cells. 2-ME induces the conversion of the microtubule-associated protein LC3-I to LC3-II, a biochemical marker of autophagy that is correlated with the formation of autophagosomes. Conversion to LC3-II is accompanied by protein degradation in 2-ME-treated cells. 2-ME does not induce autophagosome formation in normal primary human osteoblasts. In addition, 2-ME-dependent autophagosome formation in osteosarcoma cells requires ATG7 expression. Furthermore, 2-ME does not induce accumulation of autophagosomes in osteosarcoma cells that express dominant negative mutant RNA-dependent protein kinase (PKR) and are resistant to anti-proliferative and anti-tumor effects of 2-ME. Taken together, our study shows that 2-ME treatment induces PKR-dependent autophagy in osteosarcoma cells, and that autophagy could play an important role in 2-ME-mediated anti-tumor actions and in the control of osteosarcoma.
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