The Effect of Cadmium on Ovarian Adenocarcinoma Cell Lines: An Investigation of the Possible Mechanism of Action

Haley Todd / htodd@bellarmine.edu / Faculty Advisor: Mary Huff

Cadmium, a heavy metal and carcinogen, is an environmental and workplace contaminate. As a known endocrine disruptor, it can mimic the proliferative effects of estrogen and is classified as a metalloestrogen. While the proliferative effect of estrogen on cancerous cell growth has been well established, the effects of cadmium have not been fully examined. To determine if cadmium stimulates growth in two human ovarian adenocarcinoma cell lines, OVCAR-3 and SKOV-3, cells were treated for 48 hours with varying concentrations of cadmium, 0.001 µM – 10 µM, and growth was measured using a cell proliferation assay. Both cell lines showed a peak in cellular proliferation at 0.1 µM and cell death was induced at a 10 µM. Further, cadmium was shown to activate phosphorylation of ERK1/2, a key protein involved in estrogen signaling. To determine if cadmium-induced phosphorylation of ERK1/2 uses a similar signaling pathway as estrogen, inhibitors were used to block four key proteins in the estrogen signaling pathway including the estrogen receptor (α and ß), Src, EGFR, and MEK. Following treatment with each inhibitor, cells were treated with cadmium for five minutes and immunoblot analysis was used to measure the level of ERK1/2 phosphorylation. Preliminary results suggest that inhibiting the estrogen receptors α and ß does not inhibit phosphorylation of MAPK, suggesting cadmium induces cellular changes using a different pathway than estrogen. Inhibition studies that target other key proteins in the activation of ERK1/2 are still being investigated.