Inhibition of Autophagy Increases 2-Methoxyestradiol-Induced Cytotoxicity in SW1353 Chondrosarcoma Cells

Stephan Reumann, Kristen L. Shogren, Michael J Yaszemski, Avudaiappan Maran

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Chondrosarcoma is a cartilage tumor and is the second most common malignant bone cancer. Unlike many tumors, chondrosarcomas are resistant to conventional chemotherapy and radiotherapy. Autophagy is a homeostatic mechanism through which cellular proteins and organelles are subjected to lysosomal degradation and recycling. Autophagy could play a dual role in cancer by facilitating either cell death or cell survival. To determine whether autophagy plays a role in cell death in chondrosarcoma, we have studied the effect of the anti-tumor compound 2-methoxyestradiol (2-ME) in chondrosarcoma cells in culture. Transmission electron microscopy imaging indicates that 2-ME treatment leads to the accumulation of autophagosomes in human chondrosarcoma (SW1353 and Hs819T) cells. Also, 2-ME induces the conversion of microtubule-associated protein LC3-I to LC3-II, a protein marker that is correlated with the formation of autophagosomes. Our results show that siRNAs directed against ATG3 blocks 2-ME-induced autophagosome formation in chondrosarcoma cells. In addition, treatment with Bafilomycin A1 (Baf) and 3-methyladenine (3-MA), the inhibitors of autophagy, further increased the cell death in 2-ME-treated chondrosarcoma cells. Taken together, our studies demonstrate that autophagy causes resistance to cytotoxicity in chondrosarcoma cells, and the efficacy and anti-tumor effects of drugs in chondrosarcoma could be enhanced by modulating autophagy. J. Cell. Biochem. 117: 751-759, 2016.

Original languageEnglish (US)
Pages (from-to)751-759
Number of pages9
JournalJournal of Cellular Biochemistry
Volume117
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • 2-METHOXYESTRADIOL
  • AUTOPHAGY
  • CHONDROSARCOMA
  • SW1353

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Inhibition of Autophagy Increases 2-Methoxyestradiol-Induced Cytotoxicity in SW1353 Chondrosarcoma Cells'. Together they form a unique fingerprint.

  • Cite this