Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus , and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and -acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress destruction complex (YAP-Axin-GSK-TrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800039 | PMC |
| http://dx.doi.org/10.1016/j.apsb.2021.07.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Biological Evaluation of a New Biphenyl-Based Organogold(III) Complex with In Vitro and In Vivo Anticancer Activity.
J Med Chem
January 2025
Sorbonne Université, CNRS Institut Parisien de Chimie Moléculaire, IPCM, F-75005 Paris, France.
Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) -heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex bearing a 4-CF-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. was able to induce cell apoptosis but had no effect on the cell cycle.
View Article and Find Full Text PDFNoncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.
Sci Adv
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3',5'-monophosphate response element-binding protein 3-like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells.
View Article and Find Full Text PDFCurrent status and trend of global research on the pharmacological effects of emodin family: bibliometric study and visual analysis.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Emodin, as a natural active ingredient, has shown great application potential in the fields of medicine, food and cosmetics due to its unique pharmacological effects, such as anti-inflammatory, antioxidant, anti-cancer, etc. In recent years, with the development of science and technology and the increase of people's demand for natural medicine, emodin research has been paid more and more attention by the global scientific research community. The bibliometric analysis of emodin and the construction of knowledge map are still blank.
View Article and Find Full Text PDFLZZAY01 accelerated autophagy and apoptosis in colon cancer cells and improved gut microbiota in CAC mice.
Microbiol Spectr
January 2025
Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, China.
Colorectal cancer (CRC) is one of the malignant tumors globally, with high morbidity and mortality rates. The mainstay treatment of CRC includes surgery, radiotherapy, and chemotherapy. However, these treatments are associated with a high recurrence rate, poor prognosis, and highly toxic side effects.
View Article and Find Full Text PDFCopper-Catalyzed Domino Annulation of Isoselenocyanates: A Pathway to Structurally Diverse , Se-Bis-Heterocyclic, and Fused Heterocyclic Compounds.
J Org Chem
January 2025
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, People's Republic of China.
A copper-catalyzed domino addition/cyclization reaction was developed to synthesize novel benzoselenazole-linked 1,2,3-triazole and tetracyclic fused 12-benzo[4,5]selenazole[2,3-]quinazolin-12-one derivatives from isoselenocyanates. This domino reaction efficiently constructed multiple new chemical bonds in a single step, forming either four (one C-Se and three C-) or three (one C-Se and two C-) bonds. The reaction offers several key advantages, including mild conditions, broad substrate compatibility, and straightforward and safe operation.
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!