Combined treatments with AZD5363, AZD8542, curcumin or resveratrol induce death of human glioblastoma cells by suppressing the PI3K/AKT and SHH signaling pathways

Rosalinda Mejía-Rodríguez; Daniel Romero-Trejo; Rosa O González; José Segovia

doi:10.1016/j.bbrep.2023.101430

Combined treatments with AZD5363, AZD8542, curcumin or resveratrol induce death of human glioblastoma cells by suppressing the PI3K/AKT and SHH signaling pathways

Biochem Biophys Rep. 2023 Jan 20:33:101430. doi: 10.1016/j.bbrep.2023.101430. eCollection 2023 Mar.

Authors

Rosalinda Mejía-Rodríguez¹, Daniel Romero-Trejo¹, Rosa O González², José Segovia¹

Affiliations

¹ Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico.
² Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I), Mexico.

Abstract

Glioblastoma (GBM) is a very aggressive tumor that presents vascularization, necrosis and is resistant to chemotherapy and radiotherapy. Current treatments are not effective eradicating GBM, thus, there is an urgent need to develop novel therapeutic strategies against GBM. AZD5363, AZD8542, curcumin and resveratrol, are widely studied for the treatment of cancer and in the present study we explored the effects of the administration of combined treatments with AZD5363, AZD8542, curcumin or resveratrol on human GBM cells. We found that the combined treatments with AZD5363+AZD8542+Curcumin and AZD8542+Curcumin+Resveratrol inhibit the PI3K/AKT and SHH survival pathways by decreasing the activity of AKT, the reduction of the expression of SMO, pP70S6k, pS6k, GLI1, p21 and p27, and the activation of caspase-3 as a marker of apoptosis. These results provide evidence that the combined treatments AZD5363+AZD8542+Curcumin and AZD8542+Curcumin+Resveratrol have the potential to be an interesting option against GBM.

Keywords: AZD5363; AZD8542; Combined therapy; Curcumin; Glioma; Resveratrol.