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 - http://www.scopus.com/inward/record.url?scp=85092707410&partnerID=8YFLogxK
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 -
