Cysteamine Suppresses Tumor Metastasis By Inhibiting Activity Of Matrix Metalloproteases Without Inducing Toxicity In Mouse Models Of Human Ovarian Cancer

Previously, we demonstrated that cysteamine, a small molecule inhibitor of matrixmetalloproteases (MMPs), inhibited tumor invasion in vitro and metastasis in vivo in mouse models of human pancreatic and ovarian cancer. We have also shown that subcutaneous cysteamine administration improved the survival of mice with orthotopically transplanted pancreatic tumors. Herein, we examined the effect of cysteamine on total MMP activity, MMP isoforms and activity by substrate gel zymography in tumors obtained from orthotopic mouse model of human ovarian cancer. We also investigated any gastro-intestinal and general toxicity in vital organs of mice treated with the highest dose of cysteamine (250 mg/kg). We developed orthotopic tumors by injecting two human ovarian cancer cell lines in the ovary of female athymic nude mice. After 4 days of tumor implant, the mice were treated with different doses of cysteamine and followed for 5 weeks. Total MMP activity by fluorogenic substrate, MMP-2, 9 and 14 by ELISA and MMP activity by substrate gel zymography were measured in tumor lysates and compared with untreated tumors. We performed HE 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4900. doi:10.1158/1538-7445.AM2017-4900