Clioquinol targets zinc to lysosomes in human cancer cells.

@article{Yu2009ClioquinolTZ,
  title={Clioquinol targets zinc to lysosomes in human cancer cells.},
  author={Haijun Yu and Yunfeng Zhou and Stuart E. Lind and Wei-Qun Ding},
  journal={The Biochemical journal},
  year={2009},
  volume={417 1},
  pages={
          133-9
        }
}
We have previously demonstrated that clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) acts as a zinc ionophore and induces apoptosis of human cancer cells; however, the mechanisms of clioquinol/zinc-induced apoptotic cell death remain to be elucidated further. Using fluorescence-labelled probes, the present study has examined intracellular zinc distribution after clioquinol treatment in human cancer cells in order to identify cellular targets for zinc ionophores. DU 145, a human prostate cancer… 

Figures from this paper

Chloroquine Is a Zinc Ionophore

Chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity, and its cytotoxicity and induced apoptosis in A2780 cells are investigated.

Clioquinol induces autophagy in cultured astrocytes and neurons by acting as a zinc ionophore

Clioquinol induces S-phase cell cycle arrest through the elevation of the calcium level in human neurotypic SH-SY5Y cells.

The results demonstrate for the first time that an increase of intracellular calcium content is one of the mechanisms of clioquinol in the inhibition of human neurotypic SHSY-5Y cells.

The Antiparasitic Clioquinol Induces Apoptosis in Leukemia and Myeloma Cells by Inhibiting Histone Deacetylase Activity*

  • B. CaoJie Li X. Mao
  • Biology, Medicine
    The Journal of Biological Chemistry
  • 2013
It is suggested that the HDAC enzymes are targets of C Q, which provided a novel insight into the molecular mechanism of CQ in the treatment of hematological malignancies.

Clioquinol induces cytoplasmic clearance of the X-linked inhibitor of apoptosis protein (XIAP): therapeutic indication for prostate cancer.

It is demonstrated that clioquinol selectively targets and rapidly destroys transformed prostate lines without harming primary prostate epithelial cells and reveals an exciting therapeutic approach for the treatment of prostate cancer.

Clioquinol independently targets NF-kappaB and lysosome pathways in human cancer cells.

The findings of the present study indicate that clioquinol targets NF-kappaB and lysosome pathways independently, favoring further development of clioquol as a novel anticancer agent.

A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A.

The N2-acyl-2-aminoimidazole core of ZNA represents a powerful chemotype to induce cell death in cancer cells concurrently with a disruption in zinc homeostasis, which is unique and markedly more selective than other known Zn2+-interacting compounds such as clioquinol.

Anti-tumour activity of zinc ionophore pyrithione in human ovarian cancer cells through inhibition of proliferation and migration and promotion of lysosome-mitochondrial apoptosis

It is suggested that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma.

Metal ionophores – An emerging class of anticancer drugs

A biologically based classification of metal‐binding compounds is provided that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification ofMetal‐binding drugs.

Clioquinol suppresses cyclin D1 gene expression through transcriptional and post-transcriptional mechanisms.

It is demonstrated for the first time that clioquinol targets post-transcriptional steps of cyclin D1 gene expression in cancer cells, adding new insight into the understanding of its mechanisms of anticancer action.
...

References

SHOWING 1-10 OF 39 REFERENCES

Anticancer activity of the antibiotic clioquinol.

Results show that clioquinol has anticancer effects both in vitro and in vivo, and indicates that Transition metal ionophores may be a subclass of metal chelators with anticancer activity deserving of further development.

Clioquinol and docosahexaenoic acid act synergistically to kill tumor cells

Findings reveal a novel antitumor drug combination that synergistically targets major cell survival signaling pathways, and the essential role of lipid peroxidation for their action is indicated.

Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.

Intracellular free zinc levels increased in response to treatment with MGd in the absence of exogenous zinc, indicating that MGd can mobilize bound intracellular zinc.

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper.

Mechanism of apoptosis induced by a lysosomotropic agent, L-Leucyl-L-Leucine methyl ester

The activation of caspase-3-like protease links the loss of lysosomal membrane integrity to DNA fragmentation during apoptosis induced by LeuLeuOMe.

Tracing of labile zinc in live fish hepatocytes using FluoZin-3

It is shown here that the zinc probe FluoZin-3 is useful to monitor zinc fluxes during fluorescent imaging of the trout hepatic cell line D11, which suggests the involvement of thiol residues in controlling available cytosolic zinc.

Clioquinol, a therapeutic agent for Alzheimer's disease, has proteasome-inhibitory, androgen receptor-suppressing, apoptosis-inducing, and antitumor activities in human prostate cancer cells and xenografts.

This study provides strong evidence that clioquinol is able to target tumor proteasome in vivo in a copper-dependent manner, resulting in formation of an active AR inhibitor and apoptosis inducer that is responsible for its observed antiprostate tumor effect.

Silica-induced apoptosis in mouse alveolar macrophages is initiated by lysosomal enzyme activity.

Following silica exposure, lysosomal injury precedes apoptosis, and the apoptotic signaling pathway includes cathepsin D and acidic sphingomyelinase, and a role for reactive oxygen species (ROS) was investigated, but no role for ROS was apparent.

The Involvement of Bax in Zinc-Induced Mitochondrial Apoptogenesis in Malignant Prostate Cells

Evidence is provided that zinc is directly involved in facilitating a Bax-associated pore formation process that initiates mitochondrial apoptogenesis, which is enhanced by an additional effect of zinc on increasing the cellular level of Bax.

H2O2-mediated damage to lysosomal membranes of J-774 cells.

The results are interpreted as indicating generation of hydroxyl radicals within the secondary lysosomal compartment due to the occurrence of reactive ferrous iron, leading to peroxidative alterations of the lYSosomal membrane resulting in loss of lysOSomal membrane integrity with dissipation of the proton gradient and leakage of l Lysosomal contents, including hydrolytic enzymes, into the cell sap.