Cysteamine inhibits tumor invasion in vitro and metastasis in vivo in mouse models of human ovarian cancer

Authors

• A Suzuki
• P Leland
• BH Joshi
• RK Puri

Abstract

Previously, we have reported that Cysteamine, an anti-oxidant aminothiol, inhibited the tumor invasion in vitro and metastasis of pancreatic cancer in vivo in mouse models of human pancreatic cancer. We have also shown that subcutaneous Cysteamine treatment improves the survival of mice bearing orthotopically transplanted pancreatic tumors. In the present study, we examined whether Cysteamine can inhibit invasion and metastasis of other human cancers. We chose human ovarian cancer, as this tumor metastasizes intraperitoneally to visceral organs. We examined 6 human ovarian cancer cell lines and observed that Cysteamine inhibited cell invasion in vitro in a concentration-dependent manner. We measured the effect of Cysteamine on Matrix Metalloproteinases (MMPs), which are known to be involved in metastasis. Similar to invasion, MMP activity was inhibited by Cysteamine in a concentration-dependent manner. We next examined the anti-metastatic effect of Cysteamine on peritoneal metastasis in two orthotopic murine models of human ovarian cancer. A2780 and IGROV-1 ovarian tumor cells were surgically implanted orthotopically in the ovary followed by monitoring tumor growth using a high-resolution ultrasound system. Cysteamine significantly decreased the number of metastases and total weight of metastatic lesions in these mice, while the primary tumor volumes and weights were not changed. We did not observe any symptoms of general toxicity (such as general appearance, body weight, or mortality) in animals treated at the highest dose of Cysteamine. Based on these results, we conclude that Cysteamine may be a useful therapeutic agent for ovarian cancer as a mono- or combination-therapy with other anti-cancer agents.

Scientific Focus Area: Cancer Biology

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