ArticleBlood2015
Expression of executioner procaspases and their activation by a procaspase-activating compound in chronic lymphocytic leukemia cells.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- To be or not to be: navigating the influence of MicroRNAs on cervical cancer cell death.Cancer cell international · 2025Review
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.British journal of cancer · 2023Article
- Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients.Neuro-oncology · 2021Article
- Cardamonin inhibits cell proliferation by caspase-mediated cleavage of Raptor.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Design, synthesis, and evaluation of novelJournal of enzyme inhibition and medicinal chemistry · 2020Article
- Apoptotic cell-derived exosomes: messages from dying cells.Experimental & molecular medicine · 2020Review
- Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential.ACS chemical biology · 2019Review
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- Molecular Mode of Action ofInternational journal of molecular sciences · 2018Article
- Mutations in the P10 region of procaspase-8 lead to chemotherapy resistance in acute myeloid leukemia by impairing procaspase-8 dimerization.Cell death & disease · 2018Article
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- Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.ACS central science · 2016Article
- The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas.Molecular cancer therapeutics · 2016Article
- Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.Oncotarget · 2016Article
- Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.Current medicinal chemistry · 2016Article
- Preclinical combination of TP-0903, an AXL inhibitor and B-PAC-1, a procaspase-activating compound with ibrutinib in chronic lymphocytic leukemia.Leukemia & lymphoma · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Intrinsic and extrinsic apoptotic pathways converge to activate common downstream executioner caspases (caspase-3, -6, and -7), resulting in cell death. In chronic lymphocytic leukemia (CLL), neoplastic B cells evade apoptosis owing to the overexpression of survival proteins. We hypothesized that direct activation of procaspases could bypass the apoptosis resistance induced by the upstream prosurvival proteins. The procaspase-activating compounds (PAC-1), including B-PAC-1 (L14R8), convert inactive executioner procaspases to their active cleaved forms by chelation of labile zinc ions. Both at transcript and protein levels, primary CLL cells express high levels of latent procaspases (3, -7, and -9). B-PAC-1 treatment induced CLL lymphocyte death which was higher than that in normal peripheral blood mononuclear cells or B cells, and was independent of prognostic markers and microenvironmental factors. Mechanistically, B-PAC-1 treatment activated executioner procaspases and not other Zn-dependent enzymes. Exogenous zinc completely, and pancaspase inhibitors partially, reversed B-PAC-1-induced apoptosis, elucidating the zinc-mediated mechanism of action. The cell demise relied on the presence of caspase-3/7 but not caspase-8 or Bax/Bak proteins. B-PAC-1 in combination with an inhibitor of apoptosis protein antagonist (Smac066) synergistically induced apoptosis in CLL samples. Our investigations demonstrated that direct activation of executioner procaspases via B-PAC-1 treatment bypasses apoptosis resistance and is a novel approach for CLL therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.