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Mol Cancer Ther. 2019 Oct 1. pii: molcanther.0233.2019. doi: 10.1158/1535-7163.MCT-19-0233. [Epub ahead of print]

Molecular Inhibitor of QSOX1 Suppresses Tumor Growth in vivo.

Author information

1
School of Life Sciences, Arizona State University.
2
RenBio, Inc.
3
Hematology/Oncology, Mayo Clinic.
4
Assay Development, Sanford Burnham Prebys Medical Discovery Institute.
5
Department of Cancer Biology, Mayo Clinic.
6
Urology, Mayo Clinic.
7
Department of Biochemistry and Molecular Biology, Mayo Clinic.
8
Hematology/Oncology, Mayo Clinic Ho.Thai@mayo.edu.

Abstract

Quiescin Sulfhydryl Oxidase 1 (QSOX1) is an enzyme overexpressed by many different tumor types. QSOX1 catalyzes the formation of disulfide bonds in proteins. Since short hairpin knockdowns of QSOX1 have been shown to suppress tumor growth and invasion in vitro and in vivo, we hypothesized that chemical compounds inhibiting QSOX1 enzymatic activity would also suppress tumor growth, invasion, and metastasis. High throughput screening using a QSOX1-based enzymatic assay revealed multiple potential QSOX1 inhibitors. One of the inhibitors, known as "SBI-183", suppresses tumor cell growth in a Matrigel-based spheroid assay and inhibits invasion in a modified Boyden chamber, but does not affect viability of non-malignant cells. Oral administration of SBI-183 inhibits tumor growth in two independent human xenograft mouse models of renal cell carcinoma. We conclude that SBI-183 warrants further exploration as a useful tool for understanding QSOX1 biology and as a potential novel anticancer agent in tumors that overexpress QSOX1.

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