PMID- 37092860
OWN - NLM
STAT- MEDLINE
DCOM- 20230517
LR  - 20230520
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Print)
IS  - 1672-9145 (Linking)
VI  - 55
IP  - 4
DP  - 2023 Apr 19
TI  - Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 
      axis in colorectal cancer cells.
PG  - 587-600
LID - 10.3724/abbs.2023068 [doi]
AB  - Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing 
      after isolation from Chinese herbal medicine that has strong antitumor activity 
      against human tumors. However, its antitumor role remains to be elucidated. The 
      aim of this study is to explore the mechanisms underlying the tumor suppressive 
      activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 
      eliminates colorectal cancer (CRC) cells by activating gasdermin D 
      (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 
      (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. 
      GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the 
      nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in 
      turn promotes NOD-like receptor thermal protein domain associated protein 3 
      (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent 
      pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which 
      suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation 
      of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and 
      eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively 
      inhibits the proliferation of CRC cells in vitro and in nude mouse models. 
      Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in 
      CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing 
      great anticancer potential.
FAU - Wu, Yingchao
AU  - Wu Y
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Pi, Dajin
AU  - Pi D
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Zhou, Shuyao
AU  - Zhou S
AD  - College of Forestry and Landscape Architecture, South China Agricultural 
      University, Guangzhou 510642, China.
FAU - Yi, Zhongjia
AU  - Yi Z
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Dong, Yangyang
AU  - Dong Y
AD  - Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
FAU - Wang, Wuhong
AU  - Wang W
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Ye, Huan
AU  - Ye H
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Chen, Yiliu
AU  - Chen Y
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
FAU - Zuo, Qian
AU  - Zuo Q
AD  - MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional 
      Protein Research of Guangdong Higher Education Institutes, Institute of Life and 
      Health Engineering, College of Life Science and Technology, Jinan University, 
      Guangzhou 510632, China.
FAU - Ouyang, Mingzi
AU  - Ouyang M
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, 
      China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 105558-26-7 (ginsenoside Rh3)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - GAN16C9B8O (Glutathione)
RN  - 0 (STAT3 protein, human)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Pyroptosis
MH  - NF-E2-Related Factor 2/genetics
MH  - Tumor Suppressor Protein p53
MH  - *Ferroptosis
MH  - Caspase 1
MH  - Glutathione
MH  - Mice, Nude
MH  - *Colorectal Neoplasms/drug therapy
MH  - STAT3 Transcription Factor
PMC - PMC10195137
OTO - NOTNLM
OT  - Stat3/p53/NRF2 axis
OT  - colorectal cancer
OT  - ferroptosis
OT  - ginsenoside Rh3
OT  - pyroptosis
COIS- The authors declare that they have no conflict of interest.
EDAT- 2023/04/24 12:42
MHDA- 2023/05/17 06:42
PMCR- 2023/04/19
CRDT- 2023/04/24 09:13
PHST- 2023/05/17 06:42 [medline]
PHST- 2023/04/24 12:42 [pubmed]
PHST- 2023/04/24 09:13 [entrez]
PHST- 2023/04/19 00:00 [pmc-release]
AID - 10.3724/abbs.2023068 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2023 Apr 19;55(4):587-600. doi: 
      10.3724/abbs.2023068.