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Diallyl disulfide antagonizes DJ‐1 mediated proliferation, epithelial–mesenchymal transition, and chemoresistance in gastric cancer cells
Environmental Toxicology ( IF 4.5 ) Pub Date : 2024-04-20 , DOI: 10.1002/tox.24300
Jian Su 1, 2 , Hong Xia 1, 2 , Hui He 1, 3 , Huan Tang 1, 4 , Juan Zhou 1, 2 , Yi Xun 1, 5 , Fang Liu 1, 2 , Bo Su 1, 6 , Qi Su 1, 2
Affiliation  

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi‐target antitumor activity. DJ‐1 performs a vital function in promoting AKT aberrant activation via down‐regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ‐1 in epithelial–mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ‐1 in GC. Based on the identification that the correlation between high DJ‐1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down‐regulation of DJ‐1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ‐1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ‐1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ‐1‐associated drug resistance. The current study revealed that DJ‐1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

中文翻译:

二烯丙基二硫化物拮抗 DJ-1 介导的胃癌细胞增殖、上皮间质转化和化疗耐药性

二烯丙基二硫化物(DADS)是从大蒜中提取的大蒜素的有机成分,具有多靶点抗肿瘤活性。 DJ-1 通过下调肿瘤中的磷酸酶和张力蛋白同源物 (PTEN),在促进 AKT 异常激活中发挥重要作用。目前尚不清楚 DJ-1 是否参与胃癌 (GC) 细胞的上皮-间质转化 (EMT)。本研究的目的是探讨二烯丙基二硫化物 (DADS) 是否干预 DJ-1 在 GC 中的作用。基于 GC 中高 DJ-1 和低 PTEN 表达之间的相关性与临床进展有关的鉴定,我们阐明 DADS 下调 DJ-1 有助于 PTEN 表达增加和磷酸化 AKT 水平降低,这与 DJ-1 敲低和过表达细胞中显示的结果一致,同时抑制增殖、EMT、迁移和侵袭。此外,在体内实验中观察到 DADS 对 DJ-1 的拮抗作用。此外,DADS 减轻了 DJ-1 相关的耐药性。目前的研究表明DJ-1是DADS的潜在靶点之一,有望为GC的预防和辅助化疗提供有前景的策略。
更新日期:2024-04-20
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