Human NEET proteins play an important role in a variety of diseases, including cancer. Using the recently published X-ray structure of the human mNT-M1 complex, we screened a commercial chemical compound library and identified a new human mitoNEET (mNT) binding ligand (NTS-01). Biochemical investigations revealed that NTS-01 specifically binds to the human mNT protein and stabilizes its [2Fe-2S] clusters under oxidative conditions in vitro. Treatment of ovarian cancer cells with NTS-01 induces ovarian cancer (SKOV-3) mitochondrial fragmentation (fission) and reduces ovarian cancer cell proliferation in a 2D single-layer cell culture, as well as in a 3D-spheroids culture. The NTS-01 molecule represents therefore a new lead compound for further drug design studies attempting to develop efficient treatment against ovarian cancer.
Bibliographical noteFunding Information:
H.-B.M. and K.Z. were supported by the Marie Skłodowska-Curie grant agreement No. 765048. The confocal images were collected in the microscopy center from the Charles E. Smith Family and the Prof. Joel Elkes Laboratory for Collaborative Research in Psychology.
© 2022 American Chemical Society.