Effect of lathyrol derivatives on non-small cell lung cancer and the possible mechanism.
10.11817/j.issn.1672-7347.2022.210104
- Author:
Yanyan YAN
1
;
Wenmin ZHOU
2
;
Qiaoru GUO
2
;
Haiyan ZHANG
3
;
Hong JI
2
;
Luming YANG
2
;
Jianye ZHANG
4
Author Information
1. Institute of Immunology, School of Medicine, Shanxi Datong University, Datong Shanxi 037009. zwsanyan@163.com.
2. School of Pharmaceutical Sciences, Guangzhou Medical University, Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, Guangzhou 511436, China.
3. Institute of Immunology, School of Medicine, Shanxi Datong University, Datong Shanxi 037009.
4. School of Pharmaceutical Sciences, Guangzhou Medical University, Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, Guangzhou 511436, China. jianyez@163.com.
- Publication Type:Journal Article
- Keywords:
cell proliferation;
epithelial-mesenchymal transition;
invasion;
lathyrol derivatives;
migration;
non-small cell lung cancer
- MeSH:
Cadherins/genetics*;
Carcinoma, Non-Small-Cell Lung/drug therapy*;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Epithelial-Mesenchymal Transition;
Humans;
Lung Neoplasms/drug therapy*;
Matrix Metalloproteinase 2/genetics*;
RNA, Messenger;
beta Catenin/genetics*
- From:
Journal of Central South University(Medical Sciences)
2022;47(2):143-152
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells.
METHODS:Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, β-catenin, and MMP2 in A549 cells, respectively.
RESULTS:Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin β1, MMP2, MMP9, β-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, β-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05).
CONCLUSIONS:The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.
