Pancreatic cancer (PC) is among the deadliest malignancies, characterized by poor treatment response. Natural bioactive compounds, such as Morin, a flavonoid, have gained interest as potential therape Show more
Pancreatic cancer (PC) is among the deadliest malignancies, characterized by poor treatment response. Natural bioactive compounds, such as Morin, a flavonoid, have gained interest as potential therapeutic agents due to their anticancer properties but remain unexplored in PC. This study investigates the anticancer effects of Morin on PC cells, particularly its ability to induce mitophagy via the PINK1/Parkin pathway and modulate mitochondrial function and cancer stemness. PANC-1 cells were treated with Morin, and its impact on tumorigenic potential was evaluated using in vitro assays, including cell viability, colony formation, migration, invasion, and spheroid formation, as well as in vivo studies in a nude mice model. Mitochondrial function and apoptosis were assessed through flow cytometry, gene expression analysis, PCR microarrays, transmission electron microscopy (TEM), immunofluorescence, ELISA, western blotting, and molecular docking. Morin exhibited dose-dependent cytotoxicity, significantly reducing viability, colony formation, migration, and invasion in PC. It downregulated mesenchymal and stemness markers (N-cadherin, SNAI1, ZEB1, SOX2, NANOG, OCT4) while upregulating E-cadherin. Morin disrupted spheroid morphology and decreased ALDH activity, indicating reduced cancer stemness. Additionally, Morin-induced mitochondrial dysfunction, as evidenced by decreased membrane potential, ATP synthase activity, and mitochondrial mass, along with increased mitochondrial superoxide production. Upregulation of mitophagy markers (PINK1, Parkin, pAMPK, LC3A/B) and downregulation of fusion (MFN2) confirmed PINK1-mediated mitophagy. Apoptosis induction was supported by Annexin V/PI staining, TEM, elevated caspase-3/-9 levels, and cytochrome c release. Molecular docking confirmed strong Morin-PINK1 interaction. Morin induces mitophagy, promotes apoptosis, and suppresses cancer invasiveness in PC cells, highlighting its potential as an adjuvant therapeutic agent. Future clinical studies are warranted to evaluate its relevance. Show less
As human progenitor cells differentiate into neurons, the activities of many genes change; these changes are maintained within a narrow range, referred to as genome homeostasis. This process, which al Show more
As human progenitor cells differentiate into neurons, the activities of many genes change; these changes are maintained within a narrow range, referred to as genome homeostasis. This process, which alters the synchronization of the entire expressed genome, is distorted in neurodevelopmental diseases such as schizophrenia. The coordinated gene activity networks formed by altering sets of genes comprise recurring coordination modules, governed by the entropy-controlling action of nuclear FGFR1, known to be associated with DNA topology. These modules can be modeled as energy-transferring circuits, revealing that genome homeostasis is maintained by reducing oscillations (noise) in gene activity while allowing gene activity changes to be transmitted across networks; this occurs more readily in neuronal committed cells than in neural progenitors. These findings advance a model of an "entangled" global genome acting as a flexible, coordinated homeostatic system that responds to developmental signals, is governed by nuclear FGFR1, and is reprogrammed in disease. Show less