Essential oil extract p‑cresol effect on Ca2+ signaling and its underlying mechanism in DBTRG‑05MG human glioblastoma cells
Year: 2025
Type: article
Abstract: The effect of para (p)-cresol, an essential oil component, on calcium ion (Ca 2+ ) signaling in human glioblastoma is unknown.The present study aimed to investigate how p-cresol influences intracellular Ca 2+ levels ([Ca 2+ ] i ) and viability in DBTRG-05MG human glioblastoma cells.Cells were treated with p-cresol to assess its impact on cell viability and [Ca 2+ ] i .Cell viability was evaluated using a WST-1 assay.[Ca 2+ ] i was measured using a fluorescence-based Ca 2+ indicator.Cells were loaded with the Ca 2+ -sensitive dye (fura-2), and fluorescence intensity was recorded before and after p-cresol treatment to determine changes in [Ca 2+ ] i .p-Cresol induced concentration-dependent increases in [Ca 2+ ] i between 50 and 150 µM.At 50-250 µM, p-cresol triggered cell death; this effect was reversed by pretreating the cells with the Ca 2+ chelator BAPTA-AM.The removal of extracellular Ca 2+ inhibited Ca 2+ entry.p-Cresol-induced Ca 2+ influx was confirmed by Mn 2+ -induced quenching of fura-2 fluorescence.Store-operated Ca 2+ channel modulators SKF96365 and 2-aminoethoxydiphenyl borate and the protein kinase C inhibitor GF109203X inhibited p-cresol-induced Ca 2+ entry, but voltage-gated Ca 2+ channel blocker nifedipine did not.Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin in Ca 2+ -free medium inhibited p-cresol-induced [Ca 2+ ] i rises; conversely, treatment with p-cresol decreased thapsigargin-induced [Ca 2+ ] i rises.Furthermore, phospholipase C (PLC) inhibition with U73122 abolished p-cresol-induced [Ca 2+ ] i rises.In DBTRG-05MG cells, p-cresol triggered Ca 2+ -associated cell death.The process involved the entry of Ca 2+ through PKC-regulated store-operated Ca 2+ channels and release of Ca 2+ from the endoplasmic reticulum, which depends on PLC.Additionally, BAPTA-AM, which has Ca 2+ -chelating properties, may be a promising compound in preventing p-cresol-induced cytotoxicity, a potential breakthrough in neurotoxic research in glioblastoma cell model.
Source: Biomedical Reports
DOI: 10.3892/br.2025.1958
Authors: Pin-Hao Chou, Chun-Lang Su, Shih-Hau Fu, Robert Schleip, Wei-Zhe Liang
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4408154247