ArticleBritish journal of pharmacology2014
The TRPC channel blocker SKF 96365 inhibits glioblastoma cell growth by enhancing reverse mode of the Na(+) /Ca(2+) exchanger and increasing intracellular Ca(2+).
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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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
40 citing papers in PubMed, 61 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Mechanical regulation of microenvironment remodeling in brain tumors: from mechanism to therapy.Journal of neuroinflammation · 2026Review
- Differential Sensitivity of TRPC- and ORAI-Mediated Calcium Entries to 1‑[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl]imidazole Chloride (SKF-96365).ACS pharmacology & translational science · 2025Article
- TRP Channel Inhibition and NF-κB Pathway Suppression in Human Ependymal Tumor cell-line by Achillea Biebersteinii Aqueous Extract.Cell biochemistry and biophysics · 2025Article
- Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.International journal of molecular sciences · 2025Review
- Article
- Heterogeneity in Slow Synaptic Transmission Diversifies Purkinje Cell Timing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
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- CaNature communications · 2024Article
- Astroglial S100B Secretion Is Mediated by CaInternational journal of molecular sciences · 2023Article
- Role of NaInternational journal of molecular sciences · 2023Article
- TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis.Oncogenesis · 2021Article
- Review
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Effects and mechanisms of basic fibroblast growth factor on the proliferation and regenerative profiles of cryopreserved dental pulp stem cells.Cell proliferation · 2021Article
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- Development of Store-Operated Calcium Entry-Targeted Compounds in Cancer.Frontiers in pharmacology · 2021Review
- Transient Receptor Potential (TRP) Ion Channels Involved in Malignant Glioma Cell Death and Therapeutic Perspectives.Frontiers in cell and developmental biology · 2021Review
- Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype.Experimental biology and medicine (Maywood, N.J.) · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeSKF 96365 is well known for its suppressing effect on human glioblastoma growth by inhibiting pre-activated transient receptor potential canonical (TRPC) channels and Ca(2+) influx. The effect of SKF 96363 on glioblastoma cells, however, may be multifaceted and this possibility has been largely ignored. EXPERIMENTAL APPROACH: The effects of SKF 96365 on cell cycle and cell viability of cultured human glioblastoma cells were characterized. Western blot, Ca(2+) imaging and patch clamp recordings were used to delineate cell death mechanisms. siRNA gene knockdown provided additional evidence. KEY
resultsSKF 96365 repressed glioblastoma cell growth via increasing intracellular Ca(2+) ([Ca(2+) ]i ) irrespective of whether TRPC channels were blocked or not. The effect of SKF 96365 primarily resulted from enhanced reverse operation of the Na(+) /Ca(2+) exchanger (NCX) with an EC50 of 9.79 μM. SKF 96365 arrested the glioblastoma cells in the S and G2 phases and activated p38-MAPK and JNK, which were all prevented by the Ca(2+) chelator BAPTA-AM or EGTA. The expression of NCX in glioblastoma cells was significantly higher than in normal human astrocytes. Knockdown of the NCX1 isoforms diminished the effect of SKF 96365 on glioblastoma cells. CONCLUSIONS AND IMPLICATIONS: At the same concentration, SKF 96365 blocks TRPC channels and enhances the reverse mode of the NCX causing [Ca(2+) ]i accumulation and cytotoxicity. This finding suggests an alternative pharmacological mechanism of SKF 96365. It also indicates that modulation of the NCX is an effective method to disrupt Ca(2+) homeostasis and suppress human glioblastoma cells.
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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.