The antitumor activity and mechanisms of piperlongumine derivative C12 on human non-small cell lung cancer H1299 cells
10.16438/j.0513-4870.2024-0395
- VernacularTitle:荜茇酰胺衍生物C12对人非小细胞肺癌H1299细胞的抗肿瘤作用及其机制研究
- Author:
Hai-tao LONG
1
;
Xue LEI
1
;
Jia-yi CHEN
1
;
Jiao MENG
2
;
Li-hui SHAO
2
;
Zhu-rui LI
3
;
Dan-ping CHEN
1
;
Zhen-chao WANG
4
;
Yue ZHOU
3
;
Cheng-peng LI
3
Author Information
1. College of Pharmacy, Guizhou University, Guiyang 550025, China
2. National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
3. College of Pharmacy, Guizhou University, Guiyang 550025, China; Guizhou Engineering Laboratory for Synthetic Drugs, Guizhou University, Guiyang 550025, China
4. College of Pharmacy, Guizhou University, Guiyang 550025, China; Guizhou Engineering Laboratory for Synthetic Drugs, Guizhou University, Guiyang 550025, China; National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
- Publication Type:Research Article
- Keywords:
piperlongumine derivative;
H1299 cell;
proliferation;
apoptosis;
MAPK signaling pathway
- From:
Acta Pharmaceutica Sinica
2024;59(10):2773-2781
- CountryChina
- Language:Chinese
-
Abstract:
The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.
