86P Targeting signaling pathways by natural products in glioblastoma

Glioblastoma (GBM) is the most frequent and aggressive primary malignant brain tumor PI3K/Akt signaling pathway activated in almost 90% of cases. The aim this study was to evaluate capacity natural compounds potentiate activity temozolomide (TMZ) - standard pharmacological drug for GBM. U-87 MG (ATCC HTB-14) cells were treated with quercetin, resveratrol, curcumin TMZ, alone or combination TMZ either them, 30 minutes (for protein phosphorylation) 48 hours total expression). LDH-based cytotoxicity MTS assays performed dose selection. Signaling molecular patterns studies by xMAP array technology. effect treatments evaluated assessing a 9-plex panel phosphorylated proteins. Based on testing, selected working concentrations μM 15 50 temozolomide. We found strong increase JNK Thr183/Tyr185, p38 Thr180/Tyr182 STAT3 Ser727 phosphorylation moderate ERK1/2 Thr185/Tyr187 after treatment. Resveratrol treatment reduced Akt Ser473 phosphorylation, whereas other had no effect. After U87 cells, expression proteins analyzed (CREB, JNK, ERK1/2, STAT3) decreased upon products alone. When combined an even stronger decrease observed: CREB fold-regulation 0.63-0.78), NFkB (fold-regulation 0.81-0.86) 0.68-0.85). Our results revealed that quercetin resveratrol best potentiating effects expression. Natural could be used as therapeutic adjuvants GBM therapy. Given complexity pathways approaches, further are required unravel mechanisms precision