Curcumin increases efficiency of γ-irradiation in gliomas by inhibiting Hedgehog signaling pathway

Abstract

It was reported that g-irradiation had a controversial therapeutic effect on glioma cells. We aimed to investigate the cytotoxic effect on the glioma cells induced by g-irradiation and explore the treatment to rescue the phenotype alteration of remaining cells. We used transwell assay to detect the glioma cell invasion and migration capacity. Cell proliferation and apoptosis were tested by the CCK-8 assay and flow cytometry respectively. Western Blot was used to detect the activity of Hedgehog signaling pathway and Epithelial-to-Mesenchymal Transition (EMT) status. g-irradiation showed cytotoxic effect on LN229 cells in vitro, whereas this contribution was limited in U251 cells. However, it could significantly stimulated EMT process in both LN229 and U251. Curcumin (CCM) could rescue EMT process induced by g-irradiation via the suppression of Gli1 and the upregulation of Sufu. The location and expression of EMT markers were also verified by Immunofluorescence. Immunohistochemistry assay was used on intracranial glioma tissues of nude mice. The capacities of cell migration and invasion were suppressed with combined therapy. This research showed Curcumin could rescue the EMT process induced by g-irradiation via inhibiting the Hedgehog signaling pathway and potentiate the cell cytotoxic effect in vivo and in vitro.

The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

“…These nanoparticles also remarkably decreased tumor burden and increased survival of Ehrlich’s ascites carcinoma (EAC)-bearing mice [189,190]. In glioma LN229 and U251 cells, curcumin reversed the EMT process induced by γ-irradiation via the suppression of GLI1 and the upregulation of Suppressor of Fused Homolog (SUFU), as well as by suppressing the HH signaling pathway both in vitro and in vivo [191]. To nude mice carrying intracranial glioma tumor, curcumin was injected and induced MET while suppressing tumor growth [191].…”

Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment Resistance

“…A radioresistant osteosarcoma cell line clearly showed upregulation of Hh pathway and inhibition of Shh impaired its proliferation and invasive ability [ 138 ]. In glioma, RNAi against Histone deacetylase (HDAC) or a natural compound curcumin both seem to induce radiosensitivity whose actions depended on Shh pathway [ 139 , 140 ]. Pretreating hepatocellular carcinoma cell lines with Shh peptide rendered these cell lines more resistant to ionizing radiation [ 141 ].…”

Protection against gamma-radiation injury by protein tyrosine phosphatase 1B

“…Although these pathways regulate many macrophage activities, it should be expected a specific phenotype in the irradiated cells lacking PTP1B. In the same way, the Myc and the Hedgehog signaling pathways are repressed in PTP1B KO macrophages, and confirm the deficient DNA repair and the relevant pathophysiological role of macrophages after irradiation [47] , [51] , [52] . Noteworthy, the p53 and the DNA excision/repair pathways that are upregulated in the LPS condition in PTP1B KO cells are not altered after irradiation; the possibility exists that the gene changes occurred earlier than the 24 h of analysis performed in our arrays.…”