Bark of Hovenia dulcis Thunb. Suppresses Non-small Cell Lung Cancer Cells via PI3K–AKT–mTOR Pathway-mediated Apoptosis and Autophagy In vivo and In vitro
Xiao-Lan Kuang, Fan Wu, Jian-Zhan Yang, Ting Fu, Dong-Ning Shen, Bo Liu, Fang-Fang XuAbstract
Background:
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death, and the treatments are often constrained by side effects and resistance.
Objective:
This research aimed to assess the antitumor effects of
Materials and Methods:
H-TP components were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. Antitumor activity was tested in a nude mouse xenograft model. Serum metabolites were profiled using ultra-performance liquid chromatography–quadrupole/time-of-flight mass spectrometry. Effects on A549 cells were evaluated using counting kit-8, colony formation, wound healing, and Transwell assays, as well as flow cytometry, Western blot, immunofluorescence, and transmission electron microscopic analysis.
Results:
A total of 27 compounds were identified in H-TP, which significantly inhibited NSCLC tumor growth, invasion, and metastasis and induced G1-phase arrest. Mechanistically, H-TP suppressed the phosphatidylinositol 3 kinase–protein kinase B–mammalian target of rapamycin (PI3K–AKT–mTOR) pathway while upregulating Bax, cleaved caspase-3/8, LC3-II, and ATG proteins and downregulating Bcl-2 and p62, thereby promoting apoptosis and autophagy.
Conclusions:
H-TP exerts potent anti-NSCLC effects by inducing both apoptosis and autophagy via PI3K–AKT–mTOR inhibition, confirming its promising potential as a natural therapeutic candidate.