2. Academic Validation
  3. Longikaurin A induces ferroptosis and inhibits glioblastoma progression through DNA methylation - Mediated GPX4 suppression

Longikaurin A induces ferroptosis and inhibits glioblastoma progression through DNA methylation - Mediated GPX4 suppression

  • Eur J Pharmacol. 2024 Dec 5:984:177061. doi: 10.1016/j.ejphar.2024.177061.
Xiangrui Meng 1,  Qingqing Yang 2,  Yisu Gao 3,  Yawei Liu 1,  Fang Chen 2,  Wangsen Cao 4,  Guan Sun 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng, China; Yancheng Medical Research Center of Nanjing University Medical School, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China.
  • 2 Yancheng Medical Research Center of Nanjing University Medical School, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China.
  • 3 Department of Neurosurgery, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng, China.
  • 4 Yancheng Medical Research Center of Nanjing University Medical School, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China; Nanjing University Medical School, Jiangsu Key Lab of Molecular Medicine, Nanjing, China. Electronic address: wangsencao@nju.edu.cn.
  • 5 Department of Neurosurgery, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng, China; Yancheng Medical Research Center of Nanjing University Medical School, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China. Electronic address: sunguan2008@sina.com.
PMID: 39426467 DOI: 10.1016/j.ejphar.2024.177061
Abstract

Glioblastoma (GBM) is the most common primary intracranial tumor highly resistant to conventional clinical chemotherapy. Recently, the induction of Ferroptosis is emerging as a putative strategy to treat various tumors. However, the identification of the effective and applicable tumor ferroptosis-inducing agents remains challenging. In this study, we showed that longikaurin A (LK-A), a natural diterpenoid isolated from the medicinal plant Isodon ternifolius with strong anti-GBM capacities, induced remarkable GBM cell Ferroptosis along with suppressing the key anti-ferroptosis factor Glutathione Peroxidase 4 (GPX4). GPX4 promoter contains conserved CpG islands. The LK-A-induced GPX4 suppression coincided with the inhibition of ten-eleven translocation 2 (TET2), a key DNA demethylation Enzyme and an increase in the hypermethylation of the GPX4 promoter. Further, LK-A promoted the GBM ferroptotic alterations and inhibited GBM progression in both subcutaneous and orthotopic xenograft mouse models, whereas GPX4 overexpression largely abrogated its anti-GBM effects both in vitro and in vivo, suggesting that LK-A inductions of the DNA methylation-incurred GPX4 suppression and Ferroptosis are crucial for its anti-GBM functions. Together, our study has elaborated an important epigenetic pathway of GBM Ferroptosis and uncovered a critical pharmacological property of LK-A for treating GBM patients.

Keywords

DNA methylation; Ferroptosis; GPX4; Glioblastoma; LongikaurinA.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z