Anticancer effects of novel NSAIDs derivatives on cultured human glioblastoma cells

TY - JOUR

T1 - Anticancer effects of novel NSAIDs derivatives on cultured human glioblastoma cells

AU - Özdemir, Özlem

AU - Marinelli, Lisa

AU - Cacciatore, Ivana

AU - Ciulla, Michele

AU - Emsen, Bugrahan

AU - Di Stefano, Antonio

AU - Mardinoglu, Adil

AU - Turkez, Hasan

PY - 2020

Y1 - 2020

N2 - Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, α-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.

AB - Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, α-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.

KW - AKT1

KW - antiproliferative action

KW - glioblastoma

KW - NSAIDs

KW - PTEN

UR - https://www.scopus.com/pages/publications/85092707410

U2 - 10.1515/znc-2020-0093

DO - 10.1515/znc-2020-0093

M3 - Article

AN - SCOPUS:85092707410

SN - 0939-5075

JO - Zeitschrift fur Naturforschung - Section C Journal of Biosciences

JF - Zeitschrift fur Naturforschung - Section C Journal of Biosciences

ER -