Terpinen-4-ol Induces Ferroptosis of Glioma Cells via Downregulating JUN Proto-Oncogene

Abstract

According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 μM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment.

Bioinformatics identification of ferroptosis-related genes and therapeutic drugs in rheumatoid arthritis

“…Among the various mechanisms investigated in ferroptosis research, lipid peroxidation, which leads to the generation of lipid oxidation products, has garnered substantial attention. Cao et al ( 51 ) discovered that the overexpression of JUN significantly suppressed the impact of T4O on both glioma cell proliferation and ferroptosis. Luo et al ( 52 ) demonstrated that MAPK8 could reverse the impact of LINC01564 ablation on both cell apoptosis and ferroptosis.…”

Exploring the Anticancer Potential of Origanum majorana Essential Oil Monoterpenes Alone and in Combination against Non-Small Cell Lung Cancer

“…In terms of colony growth, Cao et al (2022) showed that terpinen-4-ol decreased the colony formation ability of pancreatic cells AsPC-1 and PANC-1 [17]. Furthermore, Cao et al ( 2023) corroborated the inhibitory effect of terpinen-4-ol on colony formation in glioma cancer cells U251, T98, and LN229 [22].…”

Novel approaches targeting ferroptosis in treatment of glioma

“…With the rising interest in alternative and complementary approaches to conventional cancer therapies, exploring the therapeutic potential of natural compounds is crucial. Natural compounds such as curcumin, fucoxanthin, terpinen-4-ol, Boric acid and dihydroartemisinin, have been found to possess remarkable anti-cancer properties, including the ability to induce ferroptosis (44)(45)(46)(47)(48). These compounds target ferroptosis through various mechanisms, including iron metabolism, glutathione peroxidase 4, and the cystine/glutamate antiporter system.…”