ArticleCellular oncology (Dordrecht, Netherlands)2011
Synergistic killing of colorectal cancer cells by oxaliplatin and ABT-737.
Article in Cellular oncology (Dordrecht, Netherlands), 2011. 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, 18 citations in OpenAlex.
- Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?Journal of advanced research · 2024Review
- Cancer Cell Membrane Wrapped Nanoparticles for the Delivery of a Bcl-2 Inhibitor to Triple-Negative Breast Cancer.Molecular pharmaceutics · 2023Article
- BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis.Life (Basel, Switzerland) · 2022Review
- Emerging actionable targets to treat therapy-resistant colorectal cancers.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy.Apoptosis : an international journal on programmed cell death · 2020Review
- Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC.Oncotarget · 2016Article
- Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer cells and enhances the therapeutic efficacy of BH3 mimetics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Nanoencapsulation of ABT-737 and camptothecin enhances their clinical potential through synergistic antitumor effects and reduction of systemic toxicity.Cell death & disease · 2014Article
- Targeting cell death signaling in colorectal cancer: current strategies and future perspectives.World journal of gastroenterology · 2014Review
- Pan-Bcl-2 inhibitor obatoclax delays cell cycle progression and blocks migration of colorectal cancer cells.PloS one · 2014Article
- Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.Journal of molecular signaling · 2012Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOxaliplatin is frequently used in the treatment of metastatic colorectal cancer (CRC). Our previous work shows that oxaliplatin induces the pro-apoptotic protein Noxa in CRC cells. The Bcl2-inhibitor ABT-737 is particularly effective in cells with high Noxa levels. Therefore, we tested whether oxaliplatin and ABT-737 display synergy in killing CRC cells.
methodsA panel of CRC cell lines was treated with oxaliplatin and ABT-737, either alone or in combination. Apoptosis was measured by FACS analysis of sub-G1 DNA content and by Western blot analysis of caspase-3 processing. Noxa expression was suppressed by lentiviral RNA interference.
resultsOxaliplatin and ABT-737 displayed a strong synergistic apoptotic response, which was dependent on wildtype TP53 and oncogenic KRAS. TP53 and KRAS were required for drug-induced Noxa expression and this was essential for tumor cell apoptosis. Oxaliplatin, but not ABT-737, induced p53 accumulation, but both drugs stimulated Noxa expression. Combination treatment of mice with subcutaneous tumor xenografts drastically reduced tumor volume, while single drug treatment had no effect.
conclusionABT-737 synergizes with oxaliplatin to kill colorectal cancer cells. This requires induction of Noxa by wildtype TP53 and oncogenic KRAS. Future studies should explore the anti-tumor efficacy of this drug combination in mouse models for spontaneous CRC development and in patient-derived tumor cell cultures and xenografts.
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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.