Selective Generation of Reactive Oxygen Species in Tumor Cells

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In a study reported in Clinical Cancer Research, Shin and colleagues synthesized a novel polyphenol conjugate (DPP-23) that exerted antitumor effects by targeting the unfolded protein response in the endoplasmic reticulum via production of reactive oxygen species in cancer cells but not in normal cells. The polyphenol conjugate was synthesized on the basis of quantitative structure-activity relationships, and its molecular targets were investigated using genome-wide expression profiling by DNA microarray and real-time polymerase chain reaction array.

DPP-23 was found to inhibit the growth of various tumor cells in vitro and in vivo in Balb/c nude mice xenografts. The selective generation of reactive oxygen species resulted in tumor cell death via caspase-dependent apoptosis.

The investigators concluded: “The selective generation of [reactive oxygen species] in cancer cells could be an attractive strategy for the selective killing of cancer cells, while maintaining negligible cytotoxicity to normal cells. DPP-23 represents a promising novel therapeutic agent for the selective production of [reactive oxygen species] in cancer cells.” ■

Shin SY, et al: Clin Cancer Res 20:4302-4313, 2014.




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