Unveiling the Promising Anticancer Effect of Copper-based Compounds: a Comprehensive Review

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Apr 25

PMID 38662225

Authors

Sara Abdolmaleki

Alireza Aliabadi

Samad Khaksar

Affiliations

Soon will be listed here.

Abstract

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.

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References

Sperandio S, de Belle I, Bredesen D . An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci U S A. 2000; 97(26):14376-81. PMC: 18926. DOI: 10.1073/pnas.97.26.14376. View

Saha D, Padhye S . Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti-inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex. Met Based Drugs. 2008; 8(2):73-7. PMC: 2365256. DOI: 10.1155/MBD.2001.73. View

Deegan C, McCann M, Devereux M, Coyle B, Egan D . In vitro cancer chemotherapeutic activity of 1,10-phenanthroline (phen), [Ag2(phen)3(mal)]x2H2O, [Cu(phen)2(mal)]x2H2O and [Mn(phen)2(mal)]x2H2O (malH2=malonic acid) using human cancer cells. Cancer Lett. 2006; 247(2):224-33. DOI: 10.1016/j.canlet.2006.04.006. View

Matsumoto H, Yoshii Y, Baden A, Kaneko E, Hashimoto H, Suzuki H . Preclinical Pharmacokinetic and Safety Studies of Copper-Diacetyl-Bis(N-Methylthiosemicarbazone) (Cu-ATSM): Translational Studies for Internal Radiotherapy. Transl Oncol. 2019; 12(9):1206-1212. PMC: 6600784. DOI: 10.1016/j.tranon.2019.05.017. View

Kaska W, Carrano C, Michalowski J, Jackson J, Levinson W . Inhibition of the RNA dependent DNA polymerase and the malignant transforming ability of Rous sarcoma virus by thiosemicarbazone-transition metal complexes. Bioinorg Chem. 1978; 8(3):225-36. DOI: 10.1016/s0006-3061(00)80198-2. View

Padhye S, Afrasiabi Z, Sinn E, Fok J, Mehta K, Rath N . Antitumor metallothiosemicarbazonates: structure and antitumor activity of palladium complex of phenanthrenequinone thiosemicarbazone. Inorg Chem. 2005; 44(5):1154-6. DOI: 10.1021/ic048214v. View

Fan K, Dong Y, Li T, Li Y . Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma. Front Genet. 2023; 13:1036408. PMC: 9868476. DOI: 10.3389/fgene.2022.1036408. View

Wang J, Xu M, Wang D, Li Z, Primo F, Tedesco A . Copper-Doped Carbon Dots for Optical Bioimaging and Photodynamic Therapy. Inorg Chem. 2019; 58(19):13394-13402. DOI: 10.1021/acs.inorgchem.9b02283. View

Marzano C, Pellei M, Tisato F, Santini C . Copper complexes as anticancer agents. Anticancer Agents Med Chem. 2009; 9(2):185-211. DOI: 10.2174/187152009787313837. View

10.

Adsule S, Barve V, Chen D, Ahmed F, Dou Q, Padhye S . Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J Med Chem. 2006; 49(24):7242-6. DOI: 10.1021/jm060712l. View

11.

Mhaske A, Dileep K, Kumar M, Poojary M, Pandhare K, Zhang K . ATP7A Clinical Genetics Resource - A comprehensive clinically annotated database and resource for genetic variants in ATP7A gene. Comput Struct Biotechnol J. 2020; 18:2347-2356. PMC: 7501406. DOI: 10.1016/j.csbj.2020.08.021. View

12.

Pitie M, Donnadieu B, Meunier B . Preparation of the New Bis(phenanthroline) Ligand "Clip-Phen" and Evaluation of the Nuclease Activity of the Corresponding Copper Complex. Inorg Chem. 2001; 37(14):3486-3489. DOI: 10.1021/ic980044x. View

13.

Liu T, Redalen K, Karlsen M . Development of an automated production process of [ Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications. J Labelled Comp Radiopharm. 2022; 65(7):191-202. PMC: 9321116. DOI: 10.1002/jlcr.3973. View

14.

Nam B, Lee W, Sarkar S, Kim J, Bhise A, Park H . In vivo detection of hydrogen sulfide in the brain of live mouse: application in neuroinflammation models. Eur J Nucl Med Mol Imaging. 2022; 49(12):4073-4087. DOI: 10.1007/s00259-022-05854-1. View

15.

Fernandez C, Alvarez N, Rocha A, Ellena J, Costa-Filho A, Batista A . New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents-Synthesis, Characterization and Cytotoxicity Studies-And Comparative DNA-Binding Study of Related Phen Complexes. Molecules. 2023; 28(2). PMC: 9863540. DOI: 10.3390/molecules28020896. View

16.

Saha D, Sandbhor U, Shirisha K, Padhye S, Deobagkar D, Anson C . A novel mixed-ligand antimycobacterial dimeric copper complex of ciprofloxacin and phenanthroline. Bioorg Med Chem Lett. 2004; 14(12):3027-32. DOI: 10.1016/j.bmcl.2004.04.043. View

17.

Hariprabu K, Sathya M, Vimalraj S . CRISPR/Cas9 in cancer therapy: A review with a special focus on tumor angiogenesis. Int J Biol Macromol. 2021; 192:913-930. DOI: 10.1016/j.ijbiomac.2021.10.029. View

18.

Chen C, Ma Y, Du S, Wu Y, Shen P, Yan T . Controlled CRISPR-Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy. Small. 2021; 17(33):e2101155. DOI: 10.1002/smll.202101155. View

19.

Abdolmaleki S, Khaksar S, Aliabadi A, Panjehpour A, Motieiyan E, Marabello D . Cytotoxicity and mechanism of action of metal complexes: An overview. Toxicology. 2023; 492:153516. DOI: 10.1016/j.tox.2023.153516. View

20.

Khan R, de Almeida A, Al-Farhan K, Alsalme A, Casini A, Ghazzali M . Transition-metal norharmane compounds as possible cytotoxic agents: New insights based on a coordination chemistry perspective. J Inorg Biochem. 2016; 165:128-135. DOI: 10.1016/j.jinorgbio.2016.07.001. View