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Abstract Title:

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

Abstract Source:

Free Radic Biol Med. 2022 08 20 ;189:157-168. Epub 2022 Jul 31. PMID: 35921994

Abstract Author(s):

Yangyang Tian, Zehe Ge, Miao Xu, Xin Ge, Mengjie Zhao, Fangshu Ding, Jianxing Yin, Xiuxing Wang, Yongping You, Zhumei Shi, Xu Qian

Article Affiliation:

Yangyang Tian

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.

Study Type : In Vitro Study

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