ArticleAutophagy2016
Simultaneous inhibition of the ubiquitin-proteasome system and autophagy enhances apoptosis induced by ER stress aggravators in human pancreatic cancer cells.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 92 citations in OpenAlex.
- Dual-responsive peptide nanoplatform for improved lung cancer therapy via the synergistic suppression of autophagy and drug efflux.Materials today. Bio · 2026Article
- Enhancing platinum-based chemotherapy efficacy and safety through combination therapy-mediated remodeling of autophagic homeostasis in gastric cancer.Cell death & disease · 2026Article
- A pan-cancer analysis of the oncogenic role of KDELR2 in human cancers.Discover oncology · 2025Article
- Co-assembly of natural small molecules into a carrier-free hydrogel with enhanced synergism for pancreatic cancer theranostic amplification.Materials today. Bio · 2025Article
- Review
- Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC.Translational oncology · 2025Article
- Alpha-Hederin induces incomplete autophagic injury in non-small cell lung cancer by interfering with the lysosomal acidification.Scientific reports · 2024Article
- Selenomethionine alleviates chronic heat stress-induced breast muscle injury and poor meat quality in broilers via relieving mitochondrial dysfunction and endoplasmic reticulum stress.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.Frontiers in immunology · 2024Article
- Blockade of DDR1/PYK2/ERK signaling suggesting SH2 superbinder as a novel autophagy inhibitor for pancreatic cancer.Cell death & disease · 2023Article
- Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum.Drug delivery · 2023Review
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- Hypolipidemic effect and molecular mechanism of ginsenosides: a review based on oxidative stress.Frontiers in pharmacology · 2023Review
- Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma.Scientific reports · 2022Article
- Review
- Prodigiosin inhibits cholangiocarcinoma cell proliferation and induces apoptosis via suppressing SNAREs-dependent autophagy.Cancer cell international · 2021Article
- Regulation and function of autophagy in pancreatic cancer.Autophagy · 2021Review
- Natural Products for Pancreatic Cancer Treatment: From Traditional Medicine to Modern Drug Discovery.Nutrients · 2021Review
- Kinectin1 depletion promotes EGFR degradation via the ubiquitin-proteosome system in cutaneous squamous cell carcinoma.Cell death & disease · 2021Article
- A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?Translational neurodegeneration · 2021Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
In contrast to normal tissue, cancer cells display profound alterations in protein synthesis and degradation. Therefore, proteins that regulate endoplasmic reticulum (ER) homeostasis are being increasingly recognized as potential therapeutic targets. The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. However, interactions between autophagy, the proteasome, and ER stress pathways in cancer remain largely undefined. This study demonstrated that withaferin-A (WA), the biologically active withanolide extracted from Withania somnifera, significantly increased autophagosomes, but blocked the degradation of autophagic cargo by inhibiting SNARE-mediated fusion of autophagosomes and lysosomes in human pancreatic cancer (PC) cells. WA specifically induced proteasome inhibition and promoted the accumulation of ubiquitinated proteins, which resulted in ER stress-mediated apoptosis. Meanwhile, the impaired autophagy at early stage induced by WA was likely activated in response to ER stress. Importantly, combining WA with a series of ER stress aggravators enhanced apoptosis synergistically. WA was well tolerated in mice, and displayed synergism with ER stress aggravators to inhibit tumor growth in PC xenografts. Taken together, these findings indicate that simultaneous suppression of 2 key intracellular protein degradation systems rendered PC cells vulnerable to ER stress, which may represent an avenue for new therapeutic combinations for this disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.