Abstract
BackgroundWe previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse this process and enhance the tumour sensitivity to anticancer treatment. Thus, we investigated the radiosensitization effects of clioquinol combined with zinc on HeLa and MCF-7 cells in vitro.MethodsThe dose effect of growth inhibition of clioquinol combined with zinc on cell viability was determined by a cell counting kit 8 (CCK-8) assay. The radiosensitization effect of clioquinol combined with zinc and/or MG132 in HeLa and MCF-7 cells was detected by the clonogenic assay. The cell cycle distribution and apoptosis of clioquinol combined with zinc on HeLa cells were analyzed by flow cytometry. A luciferase reporter construct was used to study the effect of clioquinol combined with zinc on NF-κB activity in HeLa cells. DNA double-strand breaks were detected by immunofluorescence. The mRNA and protein levels of ATM were analyzed by quantitative real-time PCR and Western blotting, respectively.ResultsOur research showed that clioquinol combined with zinc markedly increased the radiosensitivity of HeLa and MCF-7 cells in low toxic concentrations and resulted in a post-irradiation decrease in G2 phase arrest and an increase in apoptosis. Clioquinol combined with zinc also inhibited NF-κB activation, decreased ATM expression and increased DNA double-strand breaks (DSBs) induced by ionizing radiation.ConclusionsThese findings indicated that clioquinol combined with zinc enhanced the radiosensitivity of HeLa and MCF-7 cells by the down-regulation of ATM through the NF-κB signalling pathway.
Highlights
We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway
Clioquinol combined with zinc induces cytotoxicity in HeLa cells To evaluate the anticancer effect of CQ and zinc on cancer cells, HeLa cells were treated with different concentrations of CQ and/or zinc
Cells pretreated with 5 μM CQ and 10 μM zinc plus γray irradiation exhibited significantly lower clonogenic survival fractions at each dose than cells treated with radiation alone
Summary
We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse this process and enhance the tumour sensitivity to anticancer treatment. Zinc is a crucial trace element playing important roles in diverse physiological processes, such as growth, development, immune functions, and in the intracellular. Evolving and compelling evidence has shown that zinc is implicated as an important cytotoxic/tumour suppressor agent in several cancers. A recent meta-analysis showed that decreased zinc levels in serum and cancer tissue were found in patients with lung, head and neck, liver, stomach, and prostate cancers [5]. Serum zinc level assessment may improve cancer screening by identifying which patients should be subjected to further testing
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