Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells. The potential mechanism of the CEP-inhibited autophagy was by blockage of autophagosome-lysosome fusion and inhibition of lysosomal cathepsin B and cathepsin D maturation. Furthermore, we found for the first time that dacomitinib (DAC), a second-generation epidermal growth factor receptor inhibitor that in the phase III clinical trials for NSCLC treatment, induced a protective autophagy to decrease its anti-cancer effect. Combined treatment with CEP increased the anti-proliferative and apoptotic effects of DAC in vitro and enhanced the anti-cancer effect of DAC in NCI-H1975 xenograft mice. Collectively, CEP might be further developed as an autophagic inhibitor, and combined treatment of CEP and DAC could offer an effective strategy for NSCLC treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.canlet.2017.10.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
FTO Alleviates Hepatic Ischemia-Reperfusion Injury by Regulating Apoptosis and Autophagy.
Gastroenterol Res Pract
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Despite N-methyladenosine (mA) being closely involved in various pathophysiological processes, its potential role in liver injury is largely unknown. We designed the current research to study the potential role of fat mass and obesity-associated protein (FTO), an mA demethylase, on hepatic ischemia-reperfusion injury (IRI). Wild-type mice injected with an adeno-associated virus carrying fat mass and obesity-associated protein (AAV-FTO) or adeno-associated virus carrying green fluorescent protein (GFP) (AAV-GFP) were subjected to a hepatic IRI model in vivo.
View Article and Find Full Text PDFHypoxia-induced degradation of FTO promotes apoptosis by unmasking RACK1-mediated activation of MTK1-JNK1/2 pathway.
J Adv Res
January 2025
College of Animal Science and Technology, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China. Electronic address:
Introduction: Hypoxia, a condition characterized by inadequate oxygen supply to tissues, triggers various cellular responses, including apoptosis. The RNA demethylase FTO has been shown to exert anti-apoptotic effects, but its functions independent of RNA demethylase-particularly those involving protein-protein interactions-during hypoxia remain unclear.
Objectives: This study aimed to elucidate the cytoprotective mechanism of FTO in preventing apoptosis under hypoxic stress.
RET Inhibitor SPP86 Triggers Apoptosis and Activates the DNA Damage Response Through the Suppression of Autophagy and the PI3K/AKT Signaling Pathway in Melanoma Cells.
Drug Des Devel Ther
January 2025
The Key Laboratory of Molecular Pharmacology, Liaocheng People's Hospital, Liaocheng, Shandong, People's Republic of China.
Background: Melanoma is a highly lethal form of skin cancer, and effective treatment remains a significant challenge. SPP86 is a novel potential therapeutic drug. Nonetheless, the specific influence of SPP86 on autophagy, particularly its mechanisms in the context of DNA damage and apoptosis in human melanoma cells, remains inadequately understood.
View Article and Find Full Text PDFBisphenol A induces apoptosis and disrupts testosterone synthesis in TM3 cells via reactive oxygen species-mediated mitochondrial pathway and autophagic flux inhibition.
Ecotoxicol Environ Saf
January 2025
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin 150030, China. Electronic address:
Bisphenol A (BPA) is a common endocrine disruptor chemical that is widely used in the production of food plastic packaging, and it has been shown to potentially harm the reproductive system. However, the specific mechanism by which BPA induces apoptosis of Leydig cells (LCs) and inhibits testosterone synthesis in these cells is unclear. In the present study, TM3 cells were used as an experimental model in combination with a reactive oxygen species (ROS) scavenger (N-acetylcysteine), Caspase-3 inhibitor (Ac-DEVD-CHO), autophagy activator (Torin2), and autophagy inhibitor (Chloroquine) to investigate the potential mechanisms by which BPA causes TM3 cell damage in vitro.
View Article and Find Full Text PDFCordycepin alleviates metabolic dysfunction-associated liver disease by restoring mitochondrial homeostasis and reducing oxidative stress via Parkin-mediated mitophagy.
Biochem Pharmacol
January 2025
West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China. Electronic address:
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. The present study aims to investigate the effects and mechanisms of cordycepin on MASLD. Male C57BL/6 mice were induced with a 90-day high-fat diet (HFD) and intraperitoneal administration with streptozotocin to establish MASLD murine model.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!