PMID- 36915999
OWN - NLM
STAT- MEDLINE
DCOM- 20230315
LR  - 20230317
IS  - 1862-1783 (Electronic)
IS  - 1673-1581 (Print)
IS  - 1673-1581 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Mar 15
TI  - AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric 
      cancer.
PG  - 232-247
LID - 1673-1581(2023)03-0232-16 [pii]
LID - 10.1631/jzus.B2200351 [doi]
AB  - 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.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - She, Wenyan
AU  - She W
AD  - College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, 
      China.
FAU - Xu, Xiaoran
AU  - Xu X
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Liu, Yixin
AU  - Liu Y
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Wang, Xinyu
AU  - Wang X
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Tian, Sheng
AU  - Tian S
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Li, Shiyi
AU  - Li S
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Wang, Miao
AU  - Wang M
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Yu, Chaochao
AU  - Yu C
AD  - Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan 
      University, Wuhan University, Wuhan 430071, China.
FAU - Liu, Pan
AU  - Liu P
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China.
FAU - Huang, Tianhe
AU  - Huang T
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China. zn004593@whu.edu.cn.
FAU - Wei, Yongchang
AU  - Wei Y
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor 
      Biological Behaviors, Wuhan 430071, China. weiyongchang@whu.edu.cn.
LA  - eng
LA  - chi
GR  - ZNJC201910/the Wuhan University Zhongnan Hospital Translational Medicine and 
      Interdisciplinary Research Joint Fund/
PT  - Journal Article
TT  - AAZ2可通过靶向PDK1介导线粒体依赖的凋亡.
PL  - China
TA  - J Zhejiang Univ Sci B
JT  - Journal of Zhejiang University. Science. B
JID - 101236535
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - Humans
MH  - *Signal Transduction
MH  - *Stomach Neoplasms/drug therapy
MH  - Reactive Oxygen Species/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Apoptosis
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Cell Line, Tumor
PMC - PMC10014317
OTO - NOTNLM
OT  - Apoptosis
OT  - Gastric cancer
OT  - Glucose metabolism
OT  - N-‍(4-‍(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2)
OT  - Pyruvate dehydrogenase kinase 1 (PDK1)
OT  - Reactive oxygen species (ROS)
EDAT- 2023/03/15 06:00
MHDA- 2023/03/16 06:00
PMCR- 2023/03/15
CRDT- 2023/03/14 02:33
PHST- 2023/03/14 02:33 [entrez]
PHST- 2023/03/15 06:00 [pubmed]
PHST- 2023/03/16 06:00 [medline]
PHST- 2023/03/15 00:00 [pmc-release]
AID - 1673-1581(2023)03-0232-16 [pii]
AID - 1673-1581（2023）03-0232-16 [pii]
AID - 10.1631/jzus.B2200351 [doi]
PST - ppublish
SO  - J Zhejiang Univ Sci B. 2023 Mar 15;24(3):232-247. doi: 10.1631/jzus.B2200351.