Abstract
Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
Highlights
Chloroquine is an antimalarial drug that has been used in humans for many years [1]
Chloroquine increases zinc uptake in A2780 cells To understand whether chloroquine (Figure 1) affects zinc uptake, A2780 cells were treated with 100–300 mM chloroquine in the presence of increased concentrations of zinc chloride for 1 hour
When chloroquine was added to the culture medium intracellular zinc levels were dramatically enhanced (Figure 2A), indicating that chloroquine acts as a zinc ionophore
Summary
Chloroquine has been shown to inhibit autophagy and induce apoptosis in malignant cells and has been tested in various experimental model systems [2] and in human clinical trials [3,4]. It has been demonstrated that chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy inhibition [9], and the potential side effects of chloroquine therapy have been cautiously discussed [10,11]. This indicates that a more detailed understanding of chloroquine’s anticancer mechanism is required in order to further develop this compound into an effective anticancer agent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
