Role of Cathepsin B in Cancer Progression: A Potential Target for Coordination Compounds

Akinyemi, Amos Olalekan; Pereira, George Bueno Santana; Rocha, Fábio R.P.

doi:10.2174/1389557521666210212152937

Cited by 11 publications

(6 citation statements)

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“…In the cathepsin family, CTS-B has been founded relative to tumor angiogenesis, invasion and proliferation, immune resistance, tumor response to hypoxia, and chemotherapy resistance [11][12][13][14]. Based on the critical role of CTS-B in cancers, it is crucial to develop speci c probes to determine the CTS-B expression and activity, address their physiological functions, and further design targeting therapeutic agents [12,15,16]. Among the strategies to achieve these goals, enzyme activity-based probes (ABPs) derived from enzyme substrates have been proven as a very effective approach [17].…”

Section: Introductionmentioning

confidence: 99%

A Radioactive and Fluorescent Dual Modality Cysteine Cathepsin-B Activity-Based Probe for Cancer Theranostic

Zhou

Xiao

et al. 2023

Preprint

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Purpose: Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study set out to develop and evaluate an activity-based multi-modality theranostic agent targeting CTS-B for cancer imaging and therapy. Methods: A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multi-modality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of the BMX2 binding with the CTS-B enzyme were determined by fluorescent western blot using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG with CA074 as CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement was also performed. Then in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested. Results: BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B has a time-dependent and enzyme concentration-dependent manner. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed high tumor uptake of BMX2 and 68Ga-BMX2 and accumulated for more than 24 hours. The 90Y-BMX2 could significantly inhibit HeLa tumor growth. Conclusion: The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostic in the future.

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Section: Introductionmentioning

confidence: 99%

A Radioactive and Fluorescent Dual Modality Cysteine Cathepsin-B Activity-Based Probe for Cancer Theranostic

Zhou

Xiao

et al. 2023

Preprint

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“…Hence, large substrates can enter the active site and CTB can function as an endopeptidase. 13 Based on this principle, many prodrugs have been designed with synthetic substrates. Once they are transformed into targeted cells, CTB can recognize and cleave these substrates, which releases the payload.…”

Section: Peptides Cleaved By Ctbmentioning

confidence: 99%

Cathepsin B as a target in cancer therapy and imaging

Shen

2022

New J. Chem.

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“…This abnormal concentration can be a result of a higher protein expression achieved by a higher number of copies of this gene, transcription rates, or more stable and/or more efficient mRNA variants [ 11 ]. Since high cathepsin B levels are directly related to cancer progression, cathepsin B has been proposed as a marker in cancer patients [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition

et al. 2023

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Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (3), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound 3 showed cytotoxicity against the ACHN (0.73 ± 0.10 μM) and Hepa-1c1c7 (0.91 ± 0.08 μM) tumour cell lines. Similarly, compound 3 significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound 3 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.

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Role of Cathepsin B in Cancer Progression: A Potential Target for Coordination Compounds

Cited by 11 publications

References 0 publications

A Radioactive and Fluorescent Dual Modality Cysteine Cathepsin-B Activity-Based Probe for Cancer Theranostic

A Radioactive and Fluorescent Dual Modality Cysteine Cathepsin-B Activity-Based Probe for Cancer Theranostic

Cathepsin B as a target in cancer therapy and imaging

Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition

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