ArticleJournal of the National Cancer Institute2002
Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin.
Article in Journal of the National Cancer Institute, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Single Photon Emission Computed Tomography Tracer.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026Review
- Article
- Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins' Synthesis in Solid Cancers.Nutrients · 2022Review
- Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability.The Journal of biological chemistry · 2020Article
- Sensitization of glycoengineered interferon-β1a-resistant cancer cells by cFLIP inhibition for enhanced anti-cancer therapy.Oncotarget · 2017Article
- Article
- Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids.European journal of medicinal chemistry · 2015Article
- A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO-Cbl), a Novel Vitamin BChromatographia · 2014Article
- Immunohistochemical quantification of the vitamin B12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts.Anticancer research · 2013Article
- Pharmacokinetics of intravenous nitrosylcobalamin, an antitumor agent, in healthy Beagle dogs: a pilot study.Anticancer research · 2012Article
- Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.Investigational new drugs · 2010Article
- Nitrosylcobalamin potentiates the anti-neoplastic effects of chemotherapeutic agents via suppression of survival signaling.PloS one · 2007Article
- The return of the Scarlet Pimpernel: cobalamin in inflammation II - cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS.Journal of nutritional & environmental medicine · 2007Article
- Cobalamin in inflammation III - glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases.Journal of nutritional & environmental medicine · 2007Article
- Plasma membrane delivery, endocytosis and turnover of transcobalamin receptor in polarized human intestinal epithelial cells.The Journal of physiology · 2007Article
- Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4.Molecular and cellular biology · 2006Article
- Alternatives to current disease-modifying treatment in MS: what do we need and what can we expect in the future?Journal of neurology · 2004Review
- Suppression of NF-kappa B survival signaling by nitrosylcobalamin sensitizes neoplasms to the anti-tumor effects of Apo2L/TRAIL.The Journal of biological chemistry · 2003Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe ubiquitous plasma membrane transcobalamin II receptor (TC II-R) mediates uptake of cobalamin (Cbl; vitamin B12), an essential micronutrient. Tumors often require more Cbl than normal tissue, and increased Cbl uptake may result from increased TC II-R expression. To examine whether Cbl could therefore be used as a carrier molecule to target a chemotherapy drug, we tested an analogue of Cbl with nitric oxide as a ligand, nitrosylcobalamin (NO-Cbl). Because interferon beta (IFN-beta) has antitumor effects and increases expression of some membrane receptors, we examined whether it may enhance the effects of NO-Cbl.
methodsAntiproliferative effects of NO-Cbl were assessed in 24 normal and cancer cell lines. Xenograft tumors of human ovarian cancer NIH-OVCAR-3 cells were established in athymic nude mice, and tumor growth was monitored after treatment with NO-Cbl and IFN-beta, both individually and concomitantly. TC II-R expression and apoptosis was monitored in vitro and in vivo. RNA protection assays and mitochondrial membrane potential assays were used to distinguish the extrinsic and intrinsic apoptotic pathways, respectively.
resultsCancer cell lines were more sensitive to NO-Cbl (with ID(50)s [the dose that inhibits growth by 50%] as low as 2 microM) than normal cell lines (with ID(50)s of 85-135 microM). Single-agent NO-Cbl and IFN-beta treatment of NIH-OVCAR-3 xenografts induced tumor regression, whereas combination treatment induced tumor eradication. IFN-beta treatment increased TC II-R expression in vitro and uptake of [(57)Co]cobalamin in vivo. Compared with NIH-OVCAR-3 cells treated with NO-Cbl, cells treated with NO-Cbl and IFN-beta were more apoptotic and expressed higher mRNA levels of various apoptosis-associated genes. No changes in mitochondrial membrane potential were observed in cells treated with NO-Cbl.
conclusionNO-Cbl inhibited tumor growth in vivo by activating the extrinsic apoptotic pathway. The increased expression of TC II-R induced by IFN-beta resulted in enhanced antitumor effects with NO-Cbl both in vitro and in vivo.
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