Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells

Le-Tian Huang; Tie-Jun Li; Ming-Lin Li; Han-Yong Luo; Yi-Bing Wang; Jia-He Wang

doi:10.1186/s12906-023-03944-7

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells

BMC Complement Med Ther. 2023 Apr 24;23(1):130. doi: 10.1186/s12906-023-03944-7.

Authors

Le-Tian Huang^#¹, Tie-Jun Li^#², Ming-Lin Li³, Han-Yong Luo³, Yi-Bing Wang⁴, Jia-He Wang⁵

Affiliations

¹ Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
² Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
³ Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
⁴ Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China. ybwang@cmu.edu.cn.
⁵ Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China. wangjh1@sj-hospital.org.

^# Contributed equally.

Abstract

Background: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide.

Methods: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes.

Results: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking.

Conclusions: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Keywords: Lipidomics; Network pharmacology; Parthenolide; Phosphatidylcholine; Thyroid cancer.

MeSH terms

Humans
Lipidomics*
Molecular Docking Simulation
Network Pharmacology
Reproducibility of Results
Thyroid Cancer, Papillary
Thyroid Neoplasms* / metabolism

Substances

parthenolide