NFBTA: A Potent Cytotoxic Agent against Glioblastoma.

Hasan Turkez,Carlos Da Silva Maia Bezerra Filho,Flávio Rogério Da Nóbrega,Ozlem Ozdemir,Damião Pergentino De Sousa,Yunierkis Perez-Castillo,Eduardo Tejera,Reinaldo Nóbrega De Almeida

doi:10.3390/molecules24132411

Abstract

Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.

Highlights

Glioblastoma multiforme (GBM), the most aggressive type of glioma, is classified by the WorldHealth Organization (WHO) as a grade IV brain tumor associated with high mortality [1,2,3,4]
Our findings revealed that NFBTA presented strong anticancer potential against U87MG cells
Our results revealed that NFBTA down-regulated the genes containing AKT1, AKT2, disheveled segment polarity protein 1 (DVL1), epidermal growth factor receptor (EGFR), KRAS, and PIK3R1

Summary

Introduction

Glioblastoma multiforme (GBM), the most aggressive type of glioma, is classified by the WorldHealth Organization (WHO) as a grade IV brain tumor associated with high mortality [1,2,3,4]. Glioblastoma multiforme (GBM), the most aggressive type of glioma, is classified by the World. Despite cancer therapies, including surgery, radiotherapy, and chemotherapy, the median survival with current therapeutic options is only 14.6 months. Great efforts by several laboratories and clinics have increased this survival time by barely 2.5 months. Current treatment strategies for curing malignant gliomas, including GBM, are ineffective. With such poor outcomes, there is a great need for new and innovative therapeutic approaches to GBM [5,6,7]. Recent reports indicate that investigations in GBM at the gene level are rare. The number of gene expression studies involving genetic alterations associated

Methods

Discussion

Conclusion