Antiproliferative effect of mimosine in ovarian cancer

Abstract

3200 Objective: Iron plays a critical role in cell proliferation and survival making it a potential target for cancer therapy. Iron chelators have recently been shown to possess selective anti-neoplastic properties. Mimosine, a plant amino acid, acts as a potent iron chelator, but its use in gynecologic malignancies has yet to be tested. It is a naturally occurring plant amino acid known to arrest cell-cycle progression at the G1-S border in cultured cells. The objective of our study was to evaluate the anti-proliferative and pro-apoptotic effects of mimosine on human and rat ovarian cancer cells. Methods: Human (CaOV-3 & OvCAR) and rat (NuTu 19) ovarian cancer cell lines were treated for 24–72 hours with mimosine at varying doses ranging from 50 to 800 micro-molar concentrations. Untreated cells were used as a control. Cell viability was measured by MTS reduction assay and cell proliferation was determined by BrdU incorporation. Apoptosis was analyzed by DNA fragmentation. Iron challenge studies were performed to determine the role of iron in the cytotoxic effect of mimosine. Results: Mimosine demonstrated dose dependent anti-proliferative effects on all the ovarian cancer cells tested. Cell viability was inhibited over 70% at a dose of 200μM mimosine. Mimosine also inhibited DNA synthesis as revealed by BrdU incorporation assay. Fifty percent inhibition in DNA synthesis was observed at 100 μM dose level of mimosine. Addition of ferric ion effectively reversed the effects of mimosine, indicating that the effect of mimosine is mediated by iron chelation. In addition, mimosine induced apoptosis. DNA fragmentation analysis confirmed apoptosis. Further testing revealed mimosine to have significant dose-dependent antiproliferative effects on vulvar and cervical cancer cell lines and only a minimal effect on endometrial and colorectal cells. Conclusions: Mimosine, an iron chelator, has potent cytotoxic and anti-proliferative effects on a human and rat ovarian cancer cells. Iron challenge studies imply that the anti-proliferative effect of mimosine is mediated by iron chelation. Mimosine induced apoptosis. No significant financial relationships to disclose.