Strophanthidin Induces Apoptosis of Human Lung Adenocarcinoma Cells by Promoting TRAIL-DR5 Signaling

Bibliographic Details
Title: Strophanthidin Induces Apoptosis of Human Lung Adenocarcinoma Cells by Promoting TRAIL-DR5 Signaling
Authors: Xiao Tian, Liangzhen Gu, Fangang Zeng, Xingkai Liu, Yang Zhou, Yang Dou, Juanjuan Han, Yao Zhao, Yanyan Zhang, Qun Luo, Fuyi Wang
Source: Molecules, Vol 29, Iss 4, p 877 (2024)
Publisher Information: MDPI AG, 2024.
Publication Year: 2024
Collection: LCC:Organic chemistry
Subject Terms: strophanthidin, anticancer agent, apoptosis, Trail-DR4/5 signaling, mass spectrometry, quantitative proteomics, Organic chemistry, QD241-441
More Details: Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential anticancer agent, but the underlying mechanism of action is poorly understood. Herein, we explored the molecular mechanism by which SPTD exerts anticancer effects in A549 human lung adenocarcinoma cells by means of mass spectrometry-based quantitative proteomics in combination with bioinformatics analysis. We revealed that SPTD promoted the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2, or DR5) in A549 cells to activate caspase 3/6/8, in particular caspase 3. Consequently, the activated caspases elevated the expression level of apoptotic chromatin condensation inducer in the nucleus (ACIN1) and prelamin-A/C (LMNA), ultimately inducing apoptosis via cooperation with the SPTD-induced overexpressed barrier-to-autointegration factor 1 (Banf1). Moreover, the SPTD-induced DEPs interacted with each other to downregulate the p38 MAPK/ERK signaling, contributing to the SPTD inhibition of the growth of A549 cells. Additionally, the downregulation of collagen COL1A5 by SPTD was another anticancer benefit of SPTD through the modulation of the cell microenvironment.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1420-3049
Relation: https://www.mdpi.com/1420-3049/29/4/877; https://doaj.org/toc/1420-3049
DOI: 10.3390/molecules29040877
Access URL: https://doaj.org/article/6806d2285c3e41d4be266f2e299e0b79
Accession Number: edsdoj.6806d2285c3e41d4be266f2e299e0b79
Database: Directory of Open Access Journals
Full text is not displayed to guests.
More Details
ISSN:14203049
DOI:10.3390/molecules29040877
Published in:Molecules
Language:English