Shikonin combined with curcumin synergistically induces apoptosis of glioma cells by inhibiting the PI3K/Akt/NF-κB signaling pathway
- 1Xiaolan Clinical Institute of Shantou University Medical College, Zhongshan, Guangdong 528415, P.R. China
- 2Department of Psychological Sleep, Xiaolan People's Hospital of Zhongshan ‘The Fifth People's Hospital of Zhongshan’, Zhongshan, Guangdong 528415, P.R. China
- 3Department of Neurosurgery, Xiaolan People's Hospital of Zhongshan ‘The Fifth People's Hospital of Zhongshan’, Zhongshan, Guangdong 528415, P.R. China
Abstract
Glioblastoma (GBM) is a highly aggressive, recurrent and drug-resistant malignancy of the central nervous system, with a poor prognosis and a median survival rate of <18 months, highlighting the need for the identification of novel therapeutic approaches. The natural products shikonin and curcumin have been reported to exhibit anti-glioma properties and regulate the PI3K/Akt/NF-κB signaling pathway. However, their combined effects and the underlying molecular mechanisms remain largely unclear. Using human glioma U251 cells and U87 cells as in vitro models, cell viability was assessed by Cell Counting Kit-8 assay, colony formation was evaluated by colony formation assay and apoptosis was detected by flow cytometry and Hoechst 33258 staining. The present study found that combined treatment with shikonin and curcumin synergistically reduced cell proliferation and colony formation ability (combination index <1), enhanced apoptosis induction and exhibited relatively lower cytotoxicity toward healthy cells. Mechanistically, western blot analysis showed that the combination treatment increased the Bax/Bcl-2 ratio and elevated the protein expression levels of cleaved caspase-9, cleaved caspase-3 and cleaved-poly (ADP-ribose) polymerase, while attenuating Akt (Ser473) and IκBα (Ser32) phosphorylation, and immunofluorescence confocal microscopy revealed reduced p65 nuclear translocation. These findings suggest that shikonin and curcumin may exert synergistic anti-glioma effects in vitro through inhibition of the PI3K/Akt/NF-κB signaling axis and activation of the mitochondrial apoptotic pathway. Collectively, the present study provides preliminary cellular evidence indicating that the combination of shikonin and curcumin may represent a potential sensitizing approach for further investigation in GBM treatment.
Related
- Shikonin triggers apoptosis in lung adenocarcinoma through the FHL2-FOXO1 signaling axis
- Mild heat treatment ameliorates PCOS by activating PI3K/Akt signaling and inhibiting granulosa cell apoptosis
- Shikonin Promotes Apoptosis in Multiple Myeloma Cells Through the PKM2-AMPK-PGC1α Metabolic Axis.
- Epigallocatechin gallate and thermal cycling-stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress-induced calcium ion dysregulation and oxidative stress
- Berberine and celecoxib synergistically suppress non-small cell lung cancer with EGFR/AKT/COX-2-related signaling: network pharmacology, molecular docking and experimental validation
BibTeX
@article{zhao2026shikonin,
title = {{Shikonin combined with curcumin synergistically induces apoptosis of glioma cells by inhibiting the PI3K/Akt/NF-κB signaling pathway}},
author = {Xiaojin Zhao and Mingwen Zhang and Yongchao He and Zhihu Yu and Yichun Sun and Jiabin Zhu},
journal = {Oncology Letters},
year = {2026},
month = oct,
doi = {10.3892/ol.2026.15918},
url = {https://doi.org/10.3892/ol.2026.15918},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Shikonin combined with curcumin synergistically induces apoptosis of glioma cells by inhibiting the PI3K/Akt/NF-κB signaling pathway
AU - Xiaojin Zhao
AU - Mingwen Zhang
AU - Yongchao He
AU - Zhihu Yu
AU - Yichun Sun
AU - Jiabin Zhu
PY - 2026
DA - 2026/10/23
JO - Oncology Letters
DO - 10.3892/ol.2026.15918
UR - https://doi.org/10.3892/ol.2026.15918
AB - Glioblastoma (GBM) is a highly aggressive, recurrent and drug-resistant malignancy of the central nervous system, with a poor prognosis and a median survival rate of <18 months, highlighting the need for the identification of novel therapeutic approaches. The natural products shikonin and curcumin have been reported to exhibit anti-glioma properties and regulate the PI3K/Akt/NF-κB signaling pathway. However, their combined effects and the underlying molecular mechanisms remain largely unclear. Using human glioma U251 cells and U87 cells as in vitro models, cell viability was assessed by Cell Counting Kit-8 assay, colony formation was evaluated by colony formation assay and apoptosis was detected by flow cytometry and Hoechst 33258 staining. The present study found that combined treatment with shikonin and curcumin synergistically reduced cell proliferation and colony formation ability (combination index <1), enhanced apoptosis induction and exhibited relatively lower cytotoxicity toward healthy cells. Mechanistically, western blot analysis showed that the combination treatment increased the Bax/Bcl-2 ratio and elevated the protein expression levels of cleaved caspase-9, cleaved caspase-3 and cleaved-poly (ADP-ribose) polymerase, while attenuating Akt (Ser473) and IκBα (Ser32) phosphorylation, and immunofluorescence confocal microscopy revealed reduced p65 nuclear translocation. These findings suggest that shikonin and curcumin may exert synergistic anti-glioma effects in vitro through inhibition of the PI3K/Akt/NF-κB signaling axis and activation of the mitochondrial apoptotic pathway. Collectively, the present study provides preliminary cellular evidence indicating that the combination of shikonin and curcumin may represent a potential sensitizing approach for further investigation in GBM treatment.
SN - 1792-1074
SN - 1792-1082
ER -