Manipulating the ovarian cancer metallome

Authors

• L Amable
• E Shide

Abstract

The cellular metallome serves as an important reservoir to meet the biological needs of the cell. Recent studies have suggested that cancer cells adapt their metallome to accommodate rapid cellular growth and metabolism pathways. Thus, altering the cancer metallome may yield new avenues to target cancer and chemotherapy responsiveness. Here, we took a systematic approach to characterize the cellular metallome, as well as other cellular responses, under various metal conditions in a panel of ovarian cancer and non-cancer cell lines. In addition, sensitivity to the metal-based chemotherapy drug cisplatin in response to metal treatment was evaluated. The metallome was manipulated by treating cells with either zinc, copper, magnesium, calcium, iron, manganese, or the metal chelator tetrathiomolybdate. Cell proliferation in response to metal treatment or cisplatin was measured by WST-1 assays. Metallomes were quantitated by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) by measuring the following metals: zinc, copper, magnesium, calcium, molybdenum, manganese, iron, phosphorous, and sulfur. Cellular metal concentrations were normalized to sulfur levels. Metal treatment of ovarian cancer cells resulted in differences in cellular proliferation, uptake, and the cellular metallome. The changes in the metallome were not singular in nature as altering one metal resulted in changes in multiple metals. In terms of cisplatin sensitivity, the results suggest that metal alteration was only effective in certain cell lines. The data lend further insight into how an individual’s metallomic status, a combination of nutritional and harmful metal exposure, might result in the development and progression of cancer.

Scientific Focus Area: Molecular Biology and Biochemistry

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