ArticleCancer science2009
Bortezomib-induced apoptosis in mature T-cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl-1.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- ALK-negative anaplastic large cell lymphoma is sensitive to bortezomib through Noxa upregulation and release of Bax from Bcl-2.Haematologica · 2015Trial
- Understanding the Functional Dependence and Inhibition of the Bcl‑2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine.ACS pharmacology & translational science · 2025Article
- Targeting Acetyl-CoA Carboxylase Suppresses De Novo Lipogenesis and Tumor Cell Growth in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Bortezomib Use for a Critically Ill Patient with Angioimmunoblastic T-Cell Lymphoma.Case reports in hematology · 2022Article
- Genome-Wide Profiling of the Toxic Effect of Bortezomib on Human Esophageal Carcinoma Epithelial Cells.Technology in cancer research & treatment · 2019Article
- Cyclin-dependent kinase 9 as a potential specific molecular target in NK-cell leukemia/lymphoma.Haematologica · 2018Article
- Potent anti-tumor activity of a syringolin analog in multiple myeloma: a dual inhibitor of proteasome activity targeting β2 and β5 subunits.Oncotarget · 2018Article
- Article
- Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90.Scientific reports · 2016Article
- Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma.International journal of hematology · 2016Review
- Bortezomib-based chemotherapy to treat refractory angioimmunoblastic T-cell lymphoma: A case report and review of the literature.Oncology letters · 2016Article
- Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy.Blood cancer journal · 2015Article
- Noxa in rheumatic diseases: present understanding and future impact.Rheumatology (Oxford, England) · 2014Review
- Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system.Current cancer drug targets · 2014Review
- Targeting the ubiquitin-mediated proteasome degradation of p53 for cancer therapy.Current pharmaceutical design · 2013Review
- Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer.Journal of cell death · 2013Review
- BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma.PloS one · 2013Article
- The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
- Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma.Cancer science · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bortezomib, a proteasome inhibitor that was originally developed as an inhibitor of nuclear factor-κB pathways, is currently used for the treatment of multiple myeloma (MM) and mantle cell lymphoma (MCL). The mechanisms of action of this antitumor agent have been studied by several investigators. Here, we explore the underlying mechanisms of bortezomib-induced apoptosis in cutaneous T-cell lymphoma (CTCL) and adult T-cell leukemia/lymphoma (ATLL) at the level of mitochondrial membrane injury. In all cell lines including (KMS-12-PE [MM], HUT78 [CTCL], ATN1 [ATLL], and MT4 [ATLL]), antiapoptotic factors such as c-Flip and XIAP were downregulated after exposure to bortezomib, probably via inhibition of nuclear factor-κB signaling. In addition, among the members of the BH3-only family, upregulation of Noxa was consistently seen at both the transcriptional and protein levels in a p53-independent manner after exposure to bortezomib. Repression of Noxa by small interfering RNA partially rescued CTCL and ATLL cells from bortezomib-induced apoptosis. Immunoprecipitation assays indicated time-dependent binding of Noxa and Mcl-1 in all cell types, suggesting that functional repression of Mcl-1 led to the loss of mitochondrial outer membrane potential. Similar results were also obtained in primary tumor cells from patients with ATLL. Taken together, we conclude that bortezomib-induced apoptosis in ATLL and CTCL cells at least partly depends on the upregulation of Noxa and functional repression of Mcl-1, as is also the case in MM and malignant melanoma.
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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.