Honey Targets Ribosome Biogenesis Components to Suppress the Growth of Human Pancreatic Cancer Cells

• Published in: Cancers Vol. 16; no. 19; p. 3431
• Main Authors: Bangash, Aun Ali, Alvi, Sahir Sultan, Bangash, Muhammad Ali, Ahsan, Haider, Khan, Shiza, Shareef, Rida, Villanueva, Georgina, Bansal, Divyam, Ahmad, Mudassier, Kim, Dae Joon, Chauhan, Subhash C, Hafeez, Bilal Bin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-10-2024; MDPI
• Subjects: Antibiotics; Apoptosis; Biosynthesis; c-Myc protein; Cancer cells; Care and treatment; Cell cycle; Cell organelles; Cyclin-dependent kinases; Development and progression; Diabetes; Formation; Gene expression; Growth; Health aspects; Honey; Immunotherapy; Invasiveness; Kinases; Medical prognosis; Metabolites; Metastases; Molecular modelling; Mutation; Myc protein; Nucleoli; Oxidative stress; Pancreatic cancer; Phenotypes; Proteins; Radiation therapy; Ribonucleic acid; Ribosomes; RNA; Testing; Toxicity; Transcription factors; Yeast; United States; United States > US; pancreatic cancer (PanCa); RPA135; proliferation; honey; UBTF; apoptosis; RPA194; nucleolar stress; ribosome biogenesis
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16193431

Pancreatic cancer (PanCa) is one of the deadliest cancers, with limited therapeutic response. Various molecular oncogenic events, including dysregulation of ribosome biogenesis, are linked to the induction, progression, and metastasis of PanCa. Thus, the discovery of new therapies suppressing these oncogenic events and ribosome biogenesis could be a novel therapeutic approach for the prevention and treatment of PanCa. The current study was designed to investigate the anti-cancer effect of honey against PanCa. Our results indicated that honey markedly inhibited the growth and invasive characteristics of pancreatic cancer cells by suppressing the mRNA expression and protein levels of key components of ribosome biogenesis, including RNA Pol-I subunits (RPA194 and RPA135) along with its transcriptional regulators, i.e., UBTF and c-Myc. Honey also induced nucleolar stress in PanCa cells by reducing the expression of various nucleolar proteins (NCL, FBL, and NPM). Honey-mediated regulation on ribosome biogenesis components and nucleolar organization-associated proteins significantly arrested the cell cycle in the G2M phase and induced apoptosis in PanCa cells. These results, for the first time, demonstrated that honey, being a natural remedy, has the potential to induce apoptosis and inhibit the growth and metastatic phenotypes of PanCa by targeting ribosome biogenesis.