PMID- 36610163
OWN - NLM
STAT- MEDLINE
DCOM- 20230112
LR  - 20230112
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 109
DP  - 2023 Jan
TI  - Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing 
      glycolysis via the AKT/mTOR pathway.
PG  - 154575
LID - S0944-7113(22)00663-8 [pii]
LID - 10.1016/j.phymed.2022.154575 [doi]
AB  - BACKGROUND: High levels of glycolysis supply large quantities of energy and 
      biological macromolecular raw materials for cell proliferation. Triptolide (TP) 
      is a kind of epoxy diterpene lactone extracted from the roots, flowers, leaves, 
      or grains of the Celastraceae plant, Tripterygium wilfordii. TP has multiple 
      biological activities, including anti-inflammatory, immunologic suppression, and 
      anti-cancer effects. Nevertheless, it is little known regarding its 
      anti-intrahepatic cholangiocarcinoma (ICC) growth, and the mechanism still 
      require exploration. PURPOSE: This research explored the effect of TP on ICC 
      growth and investigated whether TP inhibits glycolysis via the AKT/mTOR pathway. 
      METHODS: Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8), 
      clonogenic assay, and flow cytometry. The underlying molecular mechanism was 
      identified by determining glucose consumption, ATP production, lactate 
      production, hexokinase (HK) and pyruvate kinase (PK) activity, and Western blot 
      analysis. A rapid ICC model of AKT/YapS127A oncogene coactivation in mice was 
      used to clarify the effect of TP treatment on tumor growth and glycolysis. 
      RESULTS: The results showed that TP treatment significantly inhibited ICC cell 
      proliferation and glycolysis in a dose- and time-dependent manner(P < 0.05). 
      Further analysis suggested that TP suppressed ICC cell glycolysis by targeting 
      AKT/mTOR signaling. Additionally, we found that TP inhibits tumor growth and 
      glycolysis in AKT/YapS127A mice(P < 0.05). CONCLUSION: Taken together, we 
      revealed that TP suppressed ICC growth by suppressing glycolysis via the AKT/mTOR 
      pathway and may provide a potential therapeutic target for ICC treatment.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Li, Li
AU  - Li L
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Wang, Chuting
AU  - Wang C
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Qiu, Zhenpeng
AU  - Qiu Z
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Deng, Dongjie
AU  - Deng D
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Chen, Xin
AU  - Chen X
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Wang, Qi
AU  - Wang Q
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Meng, Yan
AU  - Meng Y
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Zhang, Baohui
AU  - Zhang B
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
FAU - Zheng, Guohua
AU  - Zheng G
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; 
      Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry 
      of Education, Hubei University of Chinese Medicine, Wuhan 430065, China. 
      Electronic address: zgh1227@sina.com.
FAU - Hu, Junjie
AU  - Hu J
AD  - College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China. 
      Electronic address: hero0712@163.com.
LA  - eng
PT  - Journal Article
DEP - 20221121
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 19ALD1S53J (triptolide)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Diterpenes)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Diterpenes/pharmacology/therapeutic use
MH  - *Cholangiocarcinoma/metabolism
MH  - Cell Proliferation
MH  - *Bile Duct Neoplasms/drug therapy/metabolism
MH  - Bile Ducts, Intrahepatic/metabolism/pathology
MH  - Glycolysis
MH  - Cell Line, Tumor
OTO - NOTNLM
OT  - AKT/mTOR pathway
OT  - Glycolysis
OT  - Intrahepatic cholangiocarcinoma
OT  - Proliferation
OT  - Triptolide
COIS- Declaration of Competing Interest All authors declare no competing interests.
EDAT- 2023/01/08 06:00
MHDA- 2023/01/13 06:00
CRDT- 2023/01/07 18:06
PHST- 2022/07/20 00:00 [received]
PHST- 2022/11/04 00:00 [revised]
PHST- 2022/11/20 00:00 [accepted]
PHST- 2023/01/08 06:00 [pubmed]
PHST- 2023/01/13 06:00 [medline]
PHST- 2023/01/07 18:06 [entrez]
AID - S0944-7113(22)00663-8 [pii]
AID - 10.1016/j.phymed.2022.154575 [doi]
PST - ppublish
SO  - Phytomedicine. 2023 Jan;109:154575. doi: 10.1016/j.phymed.2022.154575. Epub 2022 
      Nov 21.