ArticleOncogene2003
Induction of apoptosis by enediyne antibiotic calicheamicin thetaII proceeds through a caspase-mediated mitochondrial amplification loop in an entirely Bax-dependent manner.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.Future oncology (London, England) · 2018Pooled it
- Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.Leukemia research · 2014Trial
- Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions.Cancer · 2024Review
- Review
- Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models.Nature communications · 2024Article
- Review
- CD33 Expression and Gentuzumab Ozogamicin in Acute Myeloid Leukemia: Two Sides of the Same Coin.Cancers · 2021Review
- Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment.International journal of molecular sciences · 2020Review
- DNA-PK Inhibitor, M3814, as a New Combination Partner of Mylotarg in the Treatment of Acute Myeloid Leukemia.Frontiers in oncology · 2020Article
- First-in-human, phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody-drug conjugate, in patients with advanced solid tumors.International journal of cancer · 2019Article
- Chk1 Inhibition Restores Inotuzumab Ozogamicin Citotoxicity in CD22-Positive Cells Expressing Mutant p53.Frontiers in oncology · 2019Article
- Fate of Antibody-Drug Conjugates in Cancer Cells.Journal of experimental & clinical cancer research : CR · 2018Review
- Current ADC Linker Chemistry.Pharmaceutical research · 2015Review
- Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions.Beilstein journal of organic chemistry · 2014Article
- Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin.Frontiers in bioscience (Landmark edition) · 2013Review
- Article
- Iron containing anti-tumoral agents: unexpected apoptosis-inducing activity of a ferrocene amino acid derivative.Journal of cancer research and clinical oncology · 2011Article
- The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived?British journal of clinical pharmacology · 2008Review
- Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy.BMC cancer · 2006Article
- Induction of p21CIP/WAF-1 and G2 arrest by ionizing irradiation impedes caspase-3-mediated apoptosis in human carcinoma cells.Oncogene · 2006Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calicheamicin thetaII is a member of the enediyne class of antitumor antibiotics that bind to DNA and induce apoptosis. These compounds differ, however, from conventional anticancer drugs as they bind in a sequence-specific manner noncovalently to DNA and cause sequence-selective oxidation of deoxyriboses and bending of the DNA helix. Calicheamicin is clinically employed as immunoconjugate to antibodies directed against, for example, CD33 in the case of gemtuzumab ozogamicin. Here, we show by the use of the unconjugated drug that calicheamicin-induced apoptosis is independent from death-receptor/FADD-mediated signals. Moreover, calicheamicin triggers apoptosis in a p53-independent manner as shown by the use of p53 knockout cells. Cell death proceeds via activation of mitochondrial permeability transition, cytochrome c release and activation of caspase-9 and -3. The overexpression of Bcl-x(L) or Bcl-2 strongly inhibited calicheamicin-induced apoptosis. Knockout of Bax abrogated cell death after calicheamicin treatment. Thus, the activation of mitochondria and execution of cell death occur through a fully Bax-dependent mechanism. Interestingly, caspase inhibition by the pancaspase-inhibitor zVAD-fmk interfered with mitochondrial activation by calicheamicin. This places caspase activation upstream of the mitochondria and indicates that calicheamicin-triggered apoptosis is enhanced through death receptor-independent activation of the caspase cascade, that is, an amplification loop that is required for full activation of the mitochondrial pathway.
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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.