Salidroside inhibits glioma cell migration and proliferation through CYP2E1-neuroglobin-cytochrome c mediated redox axis
4 affiliations
- 1Department of Physiology, All India Institute of Medical Sciences , ,
- 2Department of Human Genetics and Molecular Medicine, Central University of Punjab , ,
- 3Department of Pathology, All India Institute of Medical Sciences , ,
- 4Department of Neurosurgery, All India Institute of Medical Sciences , ,
Abstract
Background: Glioblastoma (GB) represents one of the most aggressive primary brain tumors characterized by poor prognosis, high relapse and resistance to conventional therapies. Salidroside, a naturally occurring glucoside derived from Rhodiola rosea, has been reported to exhibit pro-apoptotic and anti-proliferative properties across multiple cancer models; however, its mechanistic basis in glioma and its therapeutic potential remain incompletely characterized.
Methods: Neuroglobin (Ngb) protein expression was analyzed in 101 glioma brain tissue specimens and 5 normal brain tissues by western blot and immunohistochemical staining. In silico analyses of oxidized and reduced state of Ngb with salidroside was performed along with pharmacokinetics and toxicity predictions to computationally evaluate possible binding interactions and drug-like properties. Further, to determine the underlying mechanisms, in vitro assays were performed in U87MG and LN229 human glioblastoma cells treated with salidroside. MTT assay, transwell assay, Annexin V/PI staining, mitochondrial membrane potential (MMP), CYP2E1 activity, intracellular NADPH levels, Fe2+/Fe3+ ratio and markers of oxidative stress including ROS assay and lipid peroxidation were also measured. The mechanism of Ngb aided apoptosis was investigated by protein expression of Ngb, caspase 3 and cytosolic cytochrome c in glioma cells.
Results: Ngb expression in glioma tissues samples significantly downregulated with increasing tumour grade as determined by immunoreactivity and western blot analysis. In-silico analyses predicted a possible interaction of salidroside with reduced state of Ngb, In vitro studies suggested significant reduction in cell viability, migration and invasion in both U87MG and LN229 cells on supplementation with salidroside. These effects were accompanied by increased CYP2E1 activity, altered intracellular NADPH levels indicating induction of oxidative stress. Mitochondrial dysfunction, manifested as reduced MMP, elevated lipid peroxidation and increased cytosolic cytochrome c release indicated activation of intrinsic apoptotic pathway. Computational analyses additionally predicted a preferential interaction with the reduced form of Ngb, providing a mechanistic hypothesis warranting experimental validation.
Conclusion: Salidroside exerts multi-faceted anti-cancer effects in glioblastoma cells, potentially involving upregulation of Ngb levels in glioma cells, modulation of redox homeostasis, mitochondrial integrity and intrinsic apoptotic signaling.
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BibTeX
@article{panda2026salidroside,
title = {{Salidroside inhibits glioma cell migration and proliferation through CYP2E1-neuroglobin-cytochrome c mediated redox axis}},
author = {Lakshmi Priya Panda and Kalpana Barhwal and Amit Kumar and Suryanarayan Biswal and Dev Kumar Tripathy and Mukund Namdev Sable and Rabi Narayan Sahu and Gaurav Chhabra},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1929709},
url = {https://europepmc.org/article/PMC/PMC13668574},
note = {CC BY},
}
RIS
TY - JOUR
TI - Salidroside inhibits glioma cell migration and proliferation through CYP2E1-neuroglobin-cytochrome c mediated redox axis
AU - Lakshmi Priya Panda
AU - Kalpana Barhwal
AU - Amit Kumar
AU - Suryanarayan Biswal
AU - Dev Kumar Tripathy
AU - Mukund Namdev Sable
AU - Rabi Narayan Sahu
AU - Gaurav Chhabra
PY - 2026
DA - 2026/10/01
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1929709
UR - https://europepmc.org/article/PMC/PMC13668574
AB - Background: Glioblastoma (GB) represents one of the most aggressive primary brain tumors characterized by poor prognosis, high relapse and resistance to conventional therapies. Salidroside, a naturally occurring glucoside derived from Rhodiola rosea, has been reported to exhibit pro-apoptotic and anti-proliferative properties across multiple cancer models; however, its mechanistic basis in glioma and its therapeutic potential remain incompletely characterized. Methods: Neuroglobin (Ngb) protein expression was analyzed in 101 glioma brain tissue specimens and 5 normal brain tissues by western blot and immunohistochemical staining. In silico analyses of oxidized and reduced state of Ngb with salidroside was performed along with pharmacokinetics and toxicity predictions to computationally evaluate possible binding interactions and drug-like properties. Further, to determine the underlying mechanisms, in vitro assays were performed in U87MG and LN229 human glioblastoma cells treated with salidroside. MTT assay, transwell assay, Annexin V/PI staining, mitochondrial membrane potential (MMP), CYP2E1 activity, intracellular NADPH levels, Fe2+/Fe3+ ratio and markers of oxidative stress including ROS assay and lipid peroxidation were also measured. The mechanism of Ngb aided apoptosis was investigated by protein expression of Ngb, caspase 3 and cytosolic cytochrome c in glioma cells. Results: Ngb expression in glioma tissues samples significantly downregulated with increasing tumour grade as determined by immunoreactivity and western blot analysis. In-silico analyses predicted a possible interaction of salidroside with reduced state of Ngb, In vitro studies suggested significant reduction in cell viability, migration and invasion in both U87MG and LN229 cells on supplementation with salidroside. These effects were accompanied by increased CYP2E1 activity, altered intracellular NADPH levels indicating induction of oxidative stress. Mitochondrial dysfunction, manifested as reduced MMP, elevated lipid peroxidation and increased cytosolic cytochrome c release indicated activation of intrinsic apoptotic pathway. Computational analyses additionally predicted a preferential interaction with the reduced form of Ngb, providing a mechanistic hypothesis warranting experimental validation. Conclusion: Salidroside exerts multi-faceted anti-cancer effects in glioblastoma cells, potentially involving upregulation of Ngb levels in glioma cells, modulation of redox homeostasis, mitochondrial integrity and intrinsic apoptotic signaling.
SN - 2234-943X
ER -