Research Information System
METABOLIC BRAIN DISEASE, vol.38, no.2, pp.393-408, 2023 (SCI-Expanded)
Glioblastoma is one of the deadliest malignant gliomas. Capsaicin is a homovanillic acid derivative that can show anticancer efects by regulating various signaling pathways. The aim of this study is to investigate the efects of capsaicin on
cell proliferation via ferroptosis in human U87-MG and U251 glioblastoma cells. Firstly, efects of capsaicin treatment on
cell viability were determined by MTT analysis. Next, cellular-proliferation and cytotoxicity assays were determined by
analyzing bromodeoxyuridine (BrdU) and lactate dehydrogenase (LDH) activity, respectively. Following, acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPx4), 5-hydroxyeicosatetraenoic acid (5-HETE),
total oxidant status (TOS), malondialdehyde (MDA), total antioxidant status (TAS) and reduced glutathione (GSH) levels
were determined by ELISA. Additionally, ACSL4 and GPx4 mRNA and protein levels were analyzed. Capsaicin showed a
concentration-dependent anti-proliferative efects in U87-MG and U251 cells. Cell viability was decreased in the both cell
lines treated with capsaicin concentrations above 50 μM, while LDH activity increased. Treatment of 121.6, 188.5, and
237.2 μM capsaicin concentrations for 24 h indicated an increase in ACSL4, 5-HETE, TOS and MDA levels in U87-MG and
U251 cells (p<0.05). On the other hand, we found that capsaicin administration caused a decrease in BrdU, GPx4, TAS and
GSH levels in U87-MG and U251 cells (p<0.05). Besides, ACSL4 mRNA and protein levels were increased in the glioblastoma cells treated with capsaicin, whereas GPx4 mRNA and protein levels were decreased. Finally, capsaicin might be used
as a potential anticancer agent with ferroptosis-induced anti-proliferative efects in the treatment of human glioblastoma.