PMID- 37081971
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230519
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell 
      ferroptosis.
PG  - 1145407
LID - 10.3389/fphar.2023.1145407 [doi]
LID - 1145407
AB  - Background: Ferroptosis is a new form of regulated cell death characterized by 
      the accumulation of iron-dependent lipid peroxides and membrane damages. Recent 
      studies have identified an important role for cancer cell ferroptosis in 
      antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to 
      exert antitumor effects on some types of cancers. However, it remains unknown 
      whether or not PPI regulates cancer cell ferroptosis. Methods: Two types of human 
      gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft 
      models in nude mice that were treated with polyphyllin I (PPI) to observe tumor 
      growth, while cells also were cultured for in vitro studies. Ferroptosis, based 
      on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, 
      was detected using a fluorescence microscope and flow cytometer, while the 
      expression of NRF2/FTH1 was measured using Western blotting assays. Results: Here 
      we found that PPI inhibited the gastric cancer growth in vivo and in vitro while 
      increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and 
      ferrous ions in the gastric cancer cells. PPI also decreased the levels of 
      nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 
      (FTH1) in gastric cancer cells in vitro. Moreover, liproxstain-1, an inhibitor of 
      cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest 
      induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were 
      diminished by the overexpression of NRF2. Conclusion: For the first time, our 
      results have demonstrated that PPI exerts its antitumor activity on the gastric 
      cancer by, at least partially, inducing cancer cell ferroptosis via regulating 
      NRF2/FTH1 pathway. These findings may be implicated for clinical replacement 
      therapy of the gastric cancer.
CI  - Copyright (c) 2023 Zheng, Wang, Zhang, Chen, Liang, Liu, Qiu, Chen, Huang, Lu and 
      Dai.
FAU - Zheng, Fang
AU  - Zheng F
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
AD  - Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical 
      Sciences, Guangzhou, Guangdong, China.
FAU - Wang, Yeshu
AU  - Wang Y
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Zhang, Qunfang
AU  - Zhang Q
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
AD  - Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical 
      Sciences, Guangzhou, Guangdong, China.
FAU - Chen, Qiuyuan
AU  - Chen Q
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Liang, Chun-Ling
AU  - Liang CL
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Liu, Huazhen
AU  - Liu H
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Qiu, Feifei
AU  - Qiu F
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Chen, Yuchao
AU  - Chen Y
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
FAU - Huang, Haiding
AU  - Huang H
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
AD  - Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical 
      Sciences, Guangzhou, Guangdong, China.
FAU - Lu, Weihui
AU  - Lu W
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
AD  - Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical 
      Sciences, Guangzhou, Guangdong, China.
FAU - Dai, Zhenhua
AU  - Dai Z
AD  - Section of Immunology, The Second Affiliated Hospital of Guangzhou University of 
      Chinese Medicine, Guangzhou, Guangdong, China.
AD  - Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical 
      Sciences, Guangzhou, Guangdong, China.
LA  - eng
PT  - Journal Article
DEP - 20230404
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
EIN - Front Pharmacol. 2023 May 03;14:1201715. PMID: 37205909
PMC - PMC10110865
OTO - NOTNLM
OT  - NRF2
OT  - anticancer drug
OT  - ferroptosis
OT  - gastric cancer
OT  - polyphyllin I
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.
EDAT- 2023/04/21 06:41
MHDA- 2023/04/21 06:42
PMCR- 2023/04/04
CRDT- 2023/04/21 02:16
PHST- 2023/01/16 00:00 [received]
PHST- 2023/03/27 00:00 [accepted]
PHST- 2023/04/21 06:42 [medline]
PHST- 2023/04/21 06:41 [pubmed]
PHST- 2023/04/21 02:16 [entrez]
PHST- 2023/04/04 00:00 [pmc-release]
AID - 1145407 [pii]
AID - 10.3389/fphar.2023.1145407 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Apr 4;14:1145407. doi: 10.3389/fphar.2023.1145407. 
      eCollection 2023.