PMID- 33416159
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20211115
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 45
IP  - 2
DP  - 2021 Feb
TI  - Polyphyllin VII induces mitochondrial apoptosis by regulating the PP2A/AKT/DRP1 
      signaling axis in human ovarian cancer.
PG  - 513-522
LID - 10.3892/or.2020.7879 [doi]
AB  - Ovarian cancer is a gynecological malignancy with high mortality. Adjuvant 
      therapy such as chemoradiotherapy inevitably leads to side effects and drug 
      resistance. In recent years, traditional Chinese medicine has been widely studied 
      for its safety, effectiveness, and unique pharmacological effects. 
      Polyphyllin VII is an important component of Rhizoma paridis saponins, and has 
      cytotoxic effects on many types of cancer cells. The aim of the present study was 
      to evaluate the anti‑tumor activity of polyphyllin VII in human ovarian cancer 
      cells. Recent studies found that polyphyllin VII induces mitochondrial pathway 
      apoptosis by increasing mitochondrial division, but the specific mechanism was 
      unclear. The results of this study revealed that polyphyllin VII could 
      effectively induce mitochondrial dysfunction, including increased mitochondrial 
      division and reactive oxygen species (ROS) production. Notably, the mitochondrial 
      location of dynamin‑related protein 1 (DRP1) plays an important role in its 
      function. In addition, polyphyllin VII enhanced the mitochondrial localization of 
      DRP1 which is mediated by increased protein phosphatase 2A (PP2A) activity, and 
      decreased AKT activity. A specific PP2A inhibitor, LB100, attenuated 
      mitochondrial division and apoptosis in cells caused by polyphyllin VII, 
      confirming the function of the PP2A/AKT pathway in polyphyllin VII treatment. 
      Additionally, xenotransplantation experiments have also confirmed the anti‑tumor 
      effect of polyphyllin VII in vivo. Therefore, interference of the mitochondrial 
      translocation of DRP1 through PP2A/AKT pathway may be an attractive and effective 
      therapeutic approach by polyphyllin VII in ovarian cancer. This may provide new 
      strategies for polyphyllin VII in the clinical treatment of ovarian cancer.
FAU - Zhao, Liubiqi
AU  - Zhao L
AD  - Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 
      Changchun, Jilin 130041, P.R. China.
FAU - Liu, Zongyu
AU  - Liu Z
AD  - Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 
      Changchun, Jilin 130041, P.R. China.
FAU - Deng, Xinyue
AU  - Deng X
AD  - Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of 
      Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 
      130041, P.R. China.
FAU - Wang, Jiabin
AU  - Wang J
AD  - Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of 
      Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 
      130041, P.R. China.
FAU - Sun, Liankun
AU  - Sun L
AD  - Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of 
      Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 
      130041, P.R. China.
FAU - Fan, Limei
AU  - Fan L
AD  - Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 
      Changchun, Jilin 130041, P.R. China.
FAU - Zhang, Yong
AU  - Zhang Y
AD  - Department of Pathophysiology, Key Laboratory of Pathophysiology, Ministry of 
      Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 
      130041, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20201202
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (LB100)
RN  - 0 (Piperazines)
RN  - 0 (Saponins)
RN  - 0 (polyphyllin VII)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.6.5.5 (DNM1L protein, human)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Fractionation
MH  - Cell Line, Tumor
MH  - Dynamins/metabolism
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mitochondria/*drug effects/pathology
MH  - Ovarian Neoplasms/*drug therapy/pathology
MH  - Piperazines/pharmacology
MH  - Protein Phosphatase 2/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Saponins/*pharmacology/therapeutic use
MH  - Signal Transduction/drug effects
MH  - Xenograft Model Antitumor Assays
PMC - PMC7757107
OTO - NOTNLM
OT  - polyphyllinVII
OT  - PP2A
OT  - AKT
OT  - dynamin-related protein 1
OT  - ovarian cancer
EDAT- 2021/01/09 06:00
MHDA- 2021/11/16 06:00
PMCR- 2020/12/02
CRDT- 2021/01/08 08:37
PHST- 2020/05/11 00:00 [received]
PHST- 2020/10/19 00:00 [accepted]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/01/08 08:37 [entrez]
PHST- 2020/12/02 00:00 [pmc-release]
AID - or-45-02-0513 [pii]
AID - 10.3892/or.2020.7879 [doi]
PST - ppublish
SO  - Oncol Rep. 2021 Feb;45(2):513-522. doi: 10.3892/or.2020.7879. Epub 2020 Dec 2.