Back to Search Start Over

Metabolomics and integrated network pharmacology analysis reveal Tricin as the active anti-cancer component of Weijing decoction by suppression of PRKCA and sphingolipid signaling.

Authors :
Li JX
Li RZ
Sun A
Zhou H
Neher E
Yang JS
Huang JM
Zhang YZ
Jiang ZB
Liang TL
Ma LR
Wang J
Wang XR
Fan XQ
Huang J
Xie Y
Liu L
Tang L
Leung EL
Yan PY
Source :
Pharmacological research [Pharmacol Res] 2021 Sep; Vol. 171, pp. 105574. Date of Electronic Publication: 2021 Jul 25.
Publication Year :
2021

Abstract

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1096-1186
Volume :
171
Database :
MEDLINE
Journal :
Pharmacological research
Publication Type :
Academic Journal
Accession number :
34419228
Full Text :
https://doi.org/10.1016/j.phrs.2021.105574