ArticleCell death & disease2012
NOXA as critical mediator for drug combinations in polychemotherapy.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
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- Overaccumulation of p53-mediated autophagy protects against betulinic acid-induced apoptotic cell death in colorectal cancer cells.Cell death & disease · 2017Article
- Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma.PloS one · 2016Article
- Peritoneal expression of Matrilysin helps identify early post-operative recurrence of colorectal cancer.Oncotarget · 2015Article
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- Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium.PloS one · 2014Article
- Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis.Cell death & disease · 2013Article
- Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.Cell communication and signaling : CCS · 2013Article
- Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies.British journal of pharmacology · 2013Article
- In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.PloS one · 2012Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During polychemotherapy, cytotoxic drugs are given in combinations to enhance their anti-tumor effectiveness. For most drug combinations, underlying signaling mechanisms responsible for positive drug-drug interactions remain elusive. Here, we prove a decisive role for the Bcl-2 family member NOXA to mediate cell death by certain drug combinations, even if drugs were combined which acted independently from NOXA, when given alone. In proof-of-principle studies, betulinic acid, doxorubicin and vincristine induced cell death in a p53- and NOXA-independent pathway involving mitochondrial pore formation, release of cytochrome c and caspase activation. In contrast, when betulinic acid was combined with either doxorubicine or vincristine, cell death signaling changed considerably; the drug combinations clearly depended on both p53 and NOXA. Similarly and of high clinical relevance, in patient-derived childhood acute leukemia samples the drug combinations, but not the single drugs depended on p53 and NOXA, as shown by RNA interference studies in patient-derived cells. Our data emphasize that NOXA represents an important target molecule for combinations of drugs that alone do not target NOXA. NOXA might have a special role in regulating apoptosis sensitivity in the complex interplay of polychemotherapy. Deciphering the differences in signaling of single drugs and drug combinations might enable designing highly effective novel polychemotherapy regimens.
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