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ER stress and molecular targets of platinum anticancer compounds
Author(s) -
Cunningham Rachael,
DeRose Victoria
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.633.4
Subject(s) - platinum , unfolded protein response , chemistry , fight or flight response , cancer research , biochemistry , biology , apoptosis , gene , catalysis
Platinum anticancer compounds have been reported to induce ER stress responses in yeast and mammalian cancer cell lines. In this work, using modified ‘click’‐enabled Pt reagents, localization of Pt compounds in treated cells has been followed using post‐treatment fluorescent labeling. Platinum localization to both nucleoli and the ER are observed in Pt‐treated cancer cell lines. The ER stress response has been followed using Xbox1 and/or HAC1 splicing in response to platinum treatment. Finally, platinum association with proteins has been assessed using post‐treatment conjugation to biotin followed by pulldown and MS analysis. Taken together, the results of these studies show that treatment with platinum compounds induces an ER stress response, and support the hypothesis that direct targeting of ER proteins plays a role in this response. Support or Funding Information Support form the American Heart Association (predoctoral to R.C.) and the National Science Foundation (CHE‐CLP to VJD) is gratefully acknowledged.