ArticleOncogene2007
HIF-1alpha contributes to tumour-selective killing by the sigma receptor antagonist rimcazole.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
15 citing papers in PubMed, 24 citations in OpenAlex.
- Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.ACS pharmacology & translational science · 2025Review
- Review
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.Journal of medicinal chemistry · 2021Review
- Review
- Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes.Frontiers in pharmacology · 2019Review
- Sigma Receptors as Endoplasmic Reticulum Stress "Gatekeepers" and their Modulators as Emerging New Weapons in the Fight Against Cancer.Frontiers in pharmacology · 2018Review
- Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases.Journal of biomedical science · 2017Review
- Sigma Receptor (σR) Ligands with Antiproliferative and Anticancer Activity.Molecules (Basel, Switzerland) · 2017Review
- Sigma-2 Receptors Play a Role in Cellular Metabolism: Stimulation of Glycolytic Hallmarks by CM764 in Human SK-N-SH Neuroblastoma.The Journal of pharmacology and experimental therapeutics · 2016Article
- The sigma-1 receptor: a regulator of cancer cell electrical plasticity?Frontiers in physiology · 2013Article
- Neuroprotective effects of high affinity Σ1 receptor selective compounds.Brain research · 2012Article
- Cholesterol at the endoplasmic reticulum: roles of the sigma-1 receptor chaperone and implications thereof in human diseases.Sub-cellular biochemistry · 2010Review
- The pharmacology of sigma-1 receptors.Pharmacology & therapeutics · 2009Review
- Sigma-1 receptor chaperones and diseases.Central nervous system agents in medicinal chemistry · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously reported tumour-selective killing by the sigma (sigma) receptor ligand rimcazole. We now report that rimcazole elevates hypoxia inducible factor-1alpha (HIF-1alpha) protein levels under normoxic conditions in colorectal (HCT-116) and mammary carcinoma (MDA MB 231) cells but fails to induce HIF-1alpha in normal fibroblasts or mammary epithelial cells. Combining the sigma-1 agonist (+)-pentazocine with rimcazole substantially reduces the accumulation of HIF-1alpha, confirming that the effect is mediated at least partly by antagonism of sigma-1 sites. HIF-1alpha knockdown by RNA interference attenuates rimcazole-induced cell death in both cell types. Thus, the induction of HIF-1alpha by rimcazole contributes to tumour cell killing. In a comparison of HCT-116p53+/+ and HCT-116p53-/- cells, HIF-1alpha levels are consistently higher after rimcazole treatment in HCT-116p53+/+ cells. Furthermore, although rimcazole kills HCT-116p53-/- cells, it has a more potent apoptosis-inducing effect in HCT-116p53+/+ cells. This suggests that the presence of functional p53 protein may enhance death induction by rimcazole in part through greater induction of HIF-1alpha. p53 is not required, however, for the rimcazole-induced engagement of HIF-1alpha in proapoptotic mode as HIF-1alpha knockdown attenuates rimcazole-induced death to comparable extents in p53 mutant and wild-type cell systems. Knowledge of HIF-1alpha involvement may assist the re-profiling of rimcazole and other sigma ligands as cancer therapeutics.
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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.