期刊
PHYTOTHERAPY RESEARCH
卷 33, 期 6, 页码 1736-1747出版社
WILEY
DOI: 10.1002/ptr.6363
关键词
CSPG4; EGR1; furanodienone; glioblastoma; negative feedback loop
资金
- basic research projects (subject arrangement) of Shenzhen Science and Technology Program [JCYJ20170413104646428, JCYJ20170413165705083, JCYJ20170413173149177]
- National Natural Science Foundation of China [81772685]
- Shenzhen Key Laboratory of Neurosurgery [ZDSYS20140509173142601]
- international cooperation research projects of Shenzhen Science and Technology Program [GJHZ20160301163900284, GJHZ20160301163419476]
- basic research projects of Shenzhen Science and Technology Program [JCYJ20170306093243010]
Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumour. Patients with GBM respond poorly to chemotherapy and have poor survival outcomes. Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), has been shown to contribute to critical processes, such as cell survival, proliferation, and chemotherapy resistance, during glioma progression. In this study, we found that furanodienone (FUR), a diene-type sesquiterpene isolated from the rhizomes of Rhizoma curcumae, exhibited a potential cytotoxic effect on temozolomide (TMZ)-resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways. Studies investigating the mechanism demonstrated that FUR suppressed CSPG4-Akt-ERK signalling, inflammatory responses, and cytokine levels but activated caspase-dependent pathways and mitochondrial dysfunction. Furthermore, an immunofluorescence assay and a dual-luciferase reporter assay revealed that inhibition of EGR1-mediated transcription might have contributed to the FUR-dependent blockade of CSPG4 signalling and glioma cell survival. These results established a link between FUR-induced CSPG4 inhibition and the suppression of EGR1-dependent transcription. Attenuation of ERK1/2 and cytokine signalling might have generated the EGR1-dependent negative feedback loop of the CSPG4 pathway during FUR-induced apoptosis. These findings suggested that FUR could be a therapeutic candidate for the treatment of malignant glioma via targeting CSPG4 signalling.
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