Discovery and characterization of Survivin ligands

2014 Fiscal Year Final Research Report

• Project/Area Number: 25750397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KAWAMURA Tatsuro 独立行政法人理化学研究所, 長田抗生物質研究室, 基礎科学特別研究員 (60528561)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: がん / Survivin / 活性酸素種 / グルタチオン / KRAS

Outline of Final Research Achievements

Using our chemical arrays, we identified NPD926 as a Survivin ligand. We found that NPD926 induced cancer cell death, and elucidated the predominant mechanism of action underlying NPD926-induced cell death: conjugation with and depletion of cellular glutathione, and subsequent generation of reactive oxygen species (ROS), but not Survivin inhibition. NPD926 preferentially induced effects in KRAS-transformed fibroblast cells, compared with their untransformed counterparts. Furthermore, NPD926 sensitized cells to inhibitors of system xc－, a cystine-glutamate antiporter considered as a potential therapeutic target in cancers including cancer stem cells. These data show the effectiveness of a newly identified ROS inducer, which targets glutathione metabolism, in cancer treatment.

Free Research Field

ケミカルバイオロジー