AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer

Autor: Yi Li, Wenyan She, Xiaoran Xu, Yixin Liu, Xinyu Wang, Sheng Tian, Shiyi Li, Miao Wang, Chaochao Yu, Pan Liu, Tianhe Huang, Yongchang Wei
Rok vydání: 2023
Předmět:
Zdroj: J Zhejiang Univ Sci B
ISSN: 1862-1783
1673-1581
DOI: 10.1631/jzus.b2200351
Popis: Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Databáze: OpenAIRE
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