Capsaicin induces redox imbalance and ferroptosis through ACSL4/ GPx4 signaling pathways in U87‑MG and U251 glioblastoma cells

Creative Commons License

Hacıoğlu C., Kar F.

METABOLIC BRAIN DISEASE, vol.38, no.2, pp.393-408, 2023 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 38 Issue: 2
  • Publication Date: 2023
  • Doi Number: 10.1007/s11011-022-00983-w
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE
  • Page Numbers: pp.393-408
  • Kütahya Health Sciences University Affiliated: Yes


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.