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Oncol Rep. 2019 Nov 6. doi: 10.3892/or.2019.7402. [Epub ahead of print]

LQB‑118 compound inhibits migration and induces cell death in glioblastoma cells.

Author information

1
Laboratory of Cellular and Molecular Hemato‑Oncology, Program of Molecular Hemato‑Oncology, Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ 20230‑130, Brazil.
2
Chemistry Laboratory, Federal University of Rio de Janeiro (UFRJ), Macaé Campus, Rio de Janeiro, RJ 27930‑560, Brazil.
3
Bioorganic Chemistry Laboratory, Natural Products Research Institute (IPPN), Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, RJ 21941‑599, Brazil.

Abstract

Glioblastoma (GBM) is the most frequent malignant brain tumor. It represents the most aggressive astrocytoma with an overall survival of 14 months. Despite improvements in surgery techniques, radio‑ and chemotherapy, most patients present treatment resistance, recurrence and disease progression. Therefore, development of effective alternative therapies is essential to overcome treatment failure. The purpose of the study was to evaluate the antitumoral activity of the synthetic compound LQB‑118, in vitro. Monolayer and three‑dimensional (3D) cell culture systems of human‑derived GBM cell lines were used to evaluate the effect of LQB‑118 on cell viability, cell death and migration. LQB‑118 reduced cell viability as determined by MTT and trypan blue exclusion assays and promoted apoptosis in monolayer cell lines with an intrinsic temozolomide (TMZ)‑resistance profile. In 3D culture models, LQB‑118 reduced cell viability as evaluated by APH assay and inhibited cell migration while the TMZ resistance profile was maintained. Moreover, LQB‑118 reduced p38 and AKT expression and phosphorylation, whereas it reduced only the phosphorylated ERK1/2 form. LQB‑118 reduced p38 and NRF2 expression, an axis that is associated with TMZ resistance, revealing a mechanism to overcome resistance. LQB‑118 also demonstrated an additional effect when combined with ionizing radiation and cisplatin. In conclusion, the present data demonstrated that LQB‑118 maintained its effectiveness in a 3D cell conformation, which shares more similarities with the tumor mass. LQB‑118 is a promising agent for GBM treatment as monotherapy and associated with radiotherapy or cisplatin. Its effect is associated with inhibition of GBM‑related survival signaling pathways.

PMID:
31746438
DOI:
10.3892/or.2019.7402

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