PMID- 33937072
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210504
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 
      5 in Gastric Cancer Cells.
PG  - 658608
LID - 10.3389/fonc.2021.658608 [doi]
LID - 658608
AB  - Gastric cancer is a global health problem. In this study, we investigate the role 
      of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric 
      cancer cells by MTT assay. The Western blotting results showed that LCT-3d 
      modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce 
      cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was 
      observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially 
      reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen 
      Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be 
      blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The 
      results demonstrate that the elevating ROS can up-regulate the expression of DR5, 
      resulting in apoptosis via mitochondrial pathway. Although the nuclear factor 
      erythroid-2 related factor 2 (Nrf2) pathway served an important role in 
      protecting gastric cancer cells against the injury of ROS, it can't reverse 
      LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d 
      induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric 
      cancer cells. LCT-3d could be a novel lead compound for development of 
      anti-cancer activity in gastric cancer.
CI  - Copyright (c) 2021 Wang, Wu, Yu, Hu, Li, Meng, Lv, Kim, Choi, Wang, Xu and Jin.
FAU - Wang, Menglin
AU  - Wang M
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Wu, Xinxin
AU  - Wu X
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Yu, Lu
AU  - Yu L
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Hu, Zi-Yun
AU  - Hu ZY
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Li, Xiaobo
AU  - Li X
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Meng, Xia
AU  - Meng X
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Lv, Chun-Tao
AU  - Lv CT
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Kim, Gi-Young
AU  - Kim GY
AD  - Department of Marine Life Sciences, Jeju National University, Jeju, South Korea.
FAU - Choi, Yung Hyun
AU  - Choi YH
AD  - Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, 
      Busan, South Korea.
FAU - Wang, Zhengya
AU  - Wang Z
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Xu, Hai-Wei
AU  - Xu HW
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
FAU - Jin, Cheng-Yun
AU  - Jin CY
AD  - Key Laboratory of Advanced Technology for Drug Preparation, Ministry of 
      Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 
      China.
AD  - State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou 
      University, Zhengzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20210416
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8085419
OTO - NOTNLM
OT  - DR5
OT  - LCT-3d
OT  - Nrf2
OT  - apoptosis
OT  - gastric cancer
OT  - reactive oxygen species
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The reviewer JH declared a shared affiliation with one of 
      the authors, G-YK, to the handling editor at time of review.
EDAT- 2021/05/04 06:00
MHDA- 2021/05/04 06:01
PMCR- 2021/01/01
CRDT- 2021/05/03 06:20
PHST- 2021/01/26 00:00 [received]
PHST- 2021/03/22 00:00 [accepted]
PHST- 2021/05/03 06:20 [entrez]
PHST- 2021/05/04 06:00 [pubmed]
PHST- 2021/05/04 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.658608 [doi]
PST - epublish
SO  - Front Oncol. 2021 Apr 16;11:658608. doi: 10.3389/fonc.2021.658608. eCollection 
      2021.