Probing Iron-Mediated Synergistic Change of Cl– and HClO in Liver Cancer Cells with a Dual-Color Fluorescence Reporter

The ambiguous molecular mechanism remains a leading cause for the high mortality rate of liver cancer. An evident iron overload has been unveiled in liver cancer cell proliferation, which is closely related to oxidative stress. However oxidative stress-regulated chloride intracellular channel protein 1 (CLIC1) obviously increases in liver cancer cells. Cl^- is also involved in cell proliferation, and its downstream product, HClO, can induce cell carcinoma when over-generated. However, whether iron overload could mediate the variation of intracellular Cl^- and HClO is still uncharted. Herein, we present a dual-responsive fluorescence reporter MQFL-NH₂ for simultaneously visualizing the fluctuation of Cl^-/HClO at the same spot in living cells. Electrostatic binding to Cl^- effectively gave an attenuated signal with blue fluorescence, and HClO induced a sharp green fluorescence. In HL-7702 cells stimulated with iron, the blue/green dual fluorescence of MQFL-NH₂ displayed that Cl^- and HClO were elevated. In contrast, they were both reduced in iron-removed SMMC-7721 cells. Further results revealed that iron overload could promote the levels of Cl^- and HClO by up-regulating CLIC1 and myeloperoxidase. Altogether, the work will energetically contribute to grasp the molecular mechanism in iron overload-mediated pathogenesis of liver cancer.