2. Academic Validation
  3. Diallyl trisulfide sensitizes radiation therapy on glioblastoma through directly targeting thioredoxin 1

Diallyl trisulfide sensitizes radiation therapy on glioblastoma through directly targeting thioredoxin 1

  • Free Radic Biol Med. 2022 Aug 20;189:157-168. doi: 10.1016/j.freeradbiomed.2022.07.019.
Yangyang Tian 1,  Zehe Ge 1,  Miao Xu 1,  Xin Ge 1,  Mengjie Zhao 2,  Fangshu Ding 1,  Jianxing Yin 3,  Xiuxing Wang 4,  Yongping You 3,  Zhumei Shi 5,  Xu Qian 6
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
  • 2 Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neuro-Psychiatric Institute, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
  • 3 Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
  • 4 Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; National Health Commission Key Laboratory of Antibody Technologies, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
  • 5 Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
  • 6 Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address: [email protected].
PMID: 35921994 DOI: 10.1016/j.freeradbiomed.2022.07.019
Abstract

Radiotherapy is a standard-of-care treatment approach for glioblastoma (GBM) patients, but therapeutic resistance to radiotherapy remains a major challenge. Here we demonstrate that diallyl trisulfide (DATS) directly conjugates with cysteine (C) 32 and C35 (C32/35) residues of thioredoxin 1 (Trx1) through Michael addition reactions. Due to localizing in activity center of Trx1, the conjugation between DATS and C32/35 results in inhibition of Trx1 activity, therefore disturbing thioredoxin system and leading to accumulated levels of Reactive Oxygen Species (ROS). High levels of Trx1 expression are correlated with poor prognosis of glioma patients. Notably, we reveal that DATS synergistically enhances irradiation (IR)-induced ROS accumulation, Apoptosis, DNA damage, as well as inhibition of tumor growth of GBM cells. These findings highlight the potential benefits of DATS in sensitizing radiotherapy of GBM patients.

Keywords

Diallyl trisulfide; Glioblastoma; Radiotherapy; Reactive oxygen species; Thioredoxin 1; Trx1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13734
    99.85%, Thioredoxin-1 Inhibitor