ArticleBlood2005
Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo.
Article in Blood, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 55 citations in OpenAlex.
- A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- Management of Myeloma Bone Lesions.International journal of molecular sciences · 2021Review
- Proinflammatory cytokine profile is critical in autocrine GH-triggered curcumin resistance engulf by atiprimod cotreatment in MCF-7 and MDA-MB-231 breast cancer cells.Molecular biology reports · 2020Article
- Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma.International journal of molecular sciences · 2020Review
- Review
- MicroRNAs in multiple myeloma and related bone disease.Annals of translational medicine · 2015Review
- Article
- Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo.The Journal of biological chemistry · 2014Article
- Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Mouse models as a translational platform for the development of new therapeutic agents in multiple myeloma.Current cancer drug targets · 2012Review
- Role of apoptosis-inducing factor, proline dehydrogenase, and NADPH oxidase in apoptosis and oxidative stress.Cell health and cytoskeleton · 2012Article
- Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma.British journal of haematology · 2011Article
- TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells.American journal of hematology · 2010Article
- Emerging therapies for multiple myeloma.Expert opinion on emerging drugs · 2009Review
- Bone marrow microenvironment and the identification of new targets for myeloma therapy.Leukemia · 2009Review
- Article
- New frontiers in the treatment of multiple myeloma.TheScientificWorldJournal · 2006Review
- Novel treatment approaches for patients with relapsed and refractory multiple myeloma.Current treatment options in oncology · 2006Review
- Article
- Targeting PI3K and RAD51 in Barrett's adenocarcinoma: impact on DNA damage checkpoints, expression profile and tumor growth.Cancer genomics & proteomicsArticle
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine; trade name, Atiprimod) is an orally bioavailable cationic amphiphilic compound that significantly inhibits production of interleukin 6 (IL-6) and inflammation in rat arthritis and autoimmune animal models. We here characterize the effect of atiprimod on human multiple myeloma (MM) cells. Azaspirane significantly inhibited growth and induced caspase-mediated apoptosis in drug-sensitive and drug-resistant MM cell lines, as well as patient MM cells. IL-6, insulin-like growth factor 1 (IGF-1), or adherence of MM cells to bone marrow stromal cells (BMSCs) did not protect against atiprimod-induced apoptosis. Both conventional (dexamethasone, doxorubicin, melphalan) and novel (arsenic trioxide) agents augment apoptosis induced by atiprimod. Azaspirane inhibits signal transducer activator of transcription 3 (STAT3) and a PI3-K (phosphatidylinositol 3-kinase) target (Akt), but not extracellular signal-regulated kinase 1 and 2 (ERK1/2), inhibits phosphorylation triggered by IL-6, and also inhibits inhibitorkappaBalpha (IkappaBalpha) and nuclear factor kappaB (NFkappaB) p65 phosphorylation triggered by tumor necrosis factor alpha (TNF-alpha). Of importance, azaspirane inhibits both IL-6 and vascular endothelial growth factor (VEGF) secretion in BMSCs triggered by MM cell binding and also inhibits angiogenesis on human umbilical vein cells (HUVECs). Finally, azaspirane demonstrates in vivo antitumor activity against human MM cell growth in severe combined immunodeficient (SCID) mice. These results, therefore, show that azaspirane both induces MM cell apoptosis and inhibits cytokine secretion in the BM milieu, providing the framework for clinical trials to improve patient outcome in MM.
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Registered trials
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