Cell viability and collagen metabolism of MCF-7 breast cancer cells are affected by carbon monoxide released from CORM-2.

Abstract

Carbon monoxide (CO), despite its reputation as a deadly poison, is being recognized as a powerful physiological regulatory agent with potential anti-cancer properties. To harness the potential of CO towards a safe therapy, CO-Releasing Molecules (CO-RMs) have been developed. In the present study, the effects of tricarbonyldichlororuthenium(II) dimer (CORM-2) on MCF-7 breast cancer cell cultures were evaluated, with particular regard to mechanisms affecting collagen biosynthesis. In our model, CORM-2 exerted dose-dependent cytotoxic and antiproliferative effects, i.e., attenuated cell viability, induced apoptosis and reduced autophagy. Collagen biosynthesis was significantly reduced, with signs of the involvement of nuclear factor kappa B, integrin β1, insulin-like growth factor 1 and proline metabolism as the probable underlying mechanism. No effects of CO-depleted CORM-2 were found, thereby demonstrating that CORM-2 activity is associated with carbon monoxide. Additionally, it was found that CORM-2 had no influence on control fibroblasts cultures. Our results confirm both the cytotoxic and collagen-related properties of CO-releasing molecule in a breast cancer cell culture, and therefore serve to encourage further research in a pre-clinical setting. To the best of our knowledge, this study is the first to attempt to relate the effects of CORM-2 on cell viability and collagen metabolism in a cancer cell culture.