PMID- 38439187
OWN - NLM
STAT- MEDLINE
DCOM- 20240416
LR  - 20240502
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 48
IP  - 5
DP  - 2024 May
TI  - Dihydroartemisinin eliminates senescent cells by promoting autophagy-dependent 
      ferroptosis via AMPK/mTOR signaling pathway.
PG  - 726-736
LID - 10.1002/cbin.12143 [doi]
AB  - Cellular senescence is an irreversible cell-cycle arrest in response to a variety 
      of cellular stresses, which contribute to the pathogenesis of a variety of 
      age-related degenerative diseases. However, effective antisenescence strategies 
      are still lacking. Drugs that selectively target senescent cells represent an 
      intriguing therapeutic strategy to delay aging and age-related diseases. Thus, we 
      thought to investigate the effects of dihydroartemisinin (DHA) on senescent cells 
      and elucidated its mechanisms underlying aging. Stress-induced premature 
      senescence (SIPS) model was built in NIH3T3 cells using H(2)O(2) and evaluated by 
      beta-galactosidase staining. Cells were exposed to DHA and subjected to cellular 
      activity assays including viability, ferroptosis, and autophagy. The number of 
      microtubule-associated protein light-chain 3 puncta was detected by 
      immunofluorescence staining. The iron content was assessed by spectrophotometer 
      and intracellular reactive oxygen species (ROS) was measured by fluorescent probe 
      dichlorodihydrofluorescein diacetate. We found that DHA triggered senescent cell 
      death via ferroptosis. DHA accelerated ferritin degradation via promoting 
      autophagy, increasing the iron contents, promoting ROS accumulation, thus leading 
      to ferroptotic cell death in SIPS cells. In addition, autophagy inhibitor BafA1 
      preconditioning inhibited ferroptosis induced by DHA. Moreover, Atg5 silencing 
      and autophagy inhibitor BafA1 preconditioning inhibited ferroptosis induced by 
      DHA. We also revealed that the expression of p-AMP-activated protein kinase 
      (AMPK) and p-mammalian target of rapamycin (mTOR) in senescent cells was 
      downregulated. These results suggested that DHA may be a promising drug candidate 
      for clearing senescent cells by inducing autophagy-dependent ferroptosis via 
      AMPK/mTOR signaling pathway.
CI  - (c) 2024 International Federation for Cell Biology.
FAU - Wan, Xing
AU  - Wan X
AUID- ORCID: 0000-0003-0993-7927
AD  - Department of Pediatrics, School of Clinical Medicine, Southwest Medical 
      University, Luzhou, China.
AD  - Department of Pediatrics, Chengdu Third People's Hospital, Chengdu, Sichuan, 
      China.
FAU - Li, Can
AU  - Li C
AD  - Deep Underground Space Medical Center, West China Hospital, Sichuan University, 
      Chengdu, China.
FAU - Tan, Yue Hao
AU  - Tan YH
AD  - Department of Inspection Technology, Sichuan Nursing Vocational College, Chengdu, 
      China.
FAU - Zuo, Shi Qi
AU  - Zuo SQ
AD  - Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern 
      Medical University, Guangzhou, Guangdong, China.
FAU - Deng, Feng Mei
AU  - Deng FM
AD  - Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, 
      China.
FAU - Sun, Jing
AU  - Sun J
AD  - Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, 
      China.
FAU - Liu, Yi Lun
AU  - Liu YL
AD  - Department of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical 
      College, Chengdu, China.
LA  - eng
GR  - 2018YFC2002000/National Key Research and Development Program of China/
GR  - 19Z13/Project of Collaborative Innovation Center of Sichuan for Elderly Care and 
      Health/
GR  - S201913705073/Exploration and Development of Creativity Experiment Project for 
      University Students/
GR  - S202013705057/Exploration and Development of Creativity Experiment Project for 
      University Students/
PT  - Journal Article
DEP - 20240304
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Artemisinins)
RN  - 6A9O50735X (artenimol)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E1UOL152H7 (Iron)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - *Artemisinins
MH  - Autophagy
MH  - Cellular Senescence
MH  - *Ferroptosis
MH  - Hydrogen Peroxide/pharmacology
MH  - Iron
MH  - NIH 3T3 Cells
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AMPK/mTOR signaling pathways
OT  - autophagy
OT  - dihydroartemisinin
OT  - ferroptosis
OT  - senescence
EDAT- 2024/03/05 06:44
MHDA- 2024/04/16 12:43
CRDT- 2024/03/05 00:23
PHST- 2023/12/30 00:00 [revised]
PHST- 2023/10/06 00:00 [received]
PHST- 2024/02/11 00:00 [accepted]
PHST- 2024/04/16 12:43 [medline]
PHST- 2024/03/05 06:44 [pubmed]
PHST- 2024/03/05 00:23 [entrez]
AID - 10.1002/cbin.12143 [doi]
PST - ppublish
SO  - Cell Biol Int. 2024 May;48(5):726-736. doi: 10.1002/cbin.12143. Epub 2024 Mar 4.