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Inhibition of Autophagy Increases 2‐Methoxyestradiol‐Induced Cytotoxicity in SW1353 Chondrosarcoma Cells
Author(s) -
Reumann Stephan,
Shogren Kristen L.,
Yaszemski Michael J.,
Maran Avudaiappan
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25360
Subject(s) - autophagy , 2 methoxyestradiol , chondrosarcoma , cytotoxicity , chemistry , cancer research , microbiology and biotechnology , biology , biochemistry , apoptosis , medicine , in vitro , pathology
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. © 2015 Wiley Periodicals, Inc.