JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

@article{Kiziltepe2007JSKAG,
  title={JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.},
  author={Tanyel Kiziltepe and Teru Hideshima and Kenji Ishitsuka and Enrique Mar{\'i}a Ocio and Noopur S. Raje and Laurence P. Catley and C. Li and Laura J. Trudel and Hiroshi Yasui and Sonia Vallet and Jeffery L. Kutok and Dharminder Chauhan and Constantine Mitsiades and Joseph E. Saavedra and Gerald N. Wogan and Larry K. Keefer and Paul J. Shami and Kenneth C. Anderson},
  journal={Blood},
  year={2007},
  volume={110 2},
  pages={709-18}
}
Here we investigated the cytotoxicity of JS-K, a prodrug designed to release nitric oxide (NO(*)) following reaction with glutathione S-transferases, in multiple myeloma (MM). JS-K showed significant cytotoxicity in both conventional therapy-sensitive and -resistant MM cell lines, as well as patient-derived MM cells. JS-K induced apoptosis in MM cells, which was associated with PARP, caspase-8, and caspase-9 cleavage; increased Fas/CD95 expression; Mcl-1 cleavage; and Bcl-2 phosphorylation, as… CONTINUE READING
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