Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
Year: 2020
Type: article
Abstract: ) venom as anticancer agents remain largely unknown. Here, we demonstrate that honeybee venom and its major component melittin potently induce cell death, particularly in the aggressive triple-negative and HER2-enriched breast cancer subtypes. Honeybee venom and melittin suppress the activation of EGFR and HER2 by interfering with the phosphorylation of these receptors in the plasma membrane of breast carcinoma cells. Mutational studies reveal that a positively charged C-terminal melittin sequence mediates plasma membrane interaction and anticancer activity. Engineering of an RGD motif further enhances targeting of melittin to malignant cells with minimal toxicity to normal cells. Lastly, administration of melittin enhances the effect of docetaxel in suppressing breast tumor growth in an allograft model. Our work unveils a molecular mechanism underpinning the anticancer selectivity of melittin, and outlines treatment strategies to target aggressive breast cancers.
Source: npj Precision Oncology
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funders: Australian Government, National Breast Cancer Foundation, Trinity College Dublin, Department of Education and Training, Medical Research Council, Australian Research Council, National Health and Medical Research Council, Royal Holloway, University of London, ARC Industrial Transformation Training Centre for Uniquely Australian Foods
Awards: Better bees for tomorrow: A proteomic and physiological characterization of male fertility in managed versus feral honeybees in Western Australia, G1815159609, Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases, G3116515437, TARGETED EPIGENETIC REACTIVATION OF DORMANT TUMOR SUPPRESSORS: NEW PRECISION THERAPIES FOR LIVER CANCER., EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER, REVERSING EPITHELIAL TO MESENCHYMAL TRANSITION BY TARGETED EPIGENETIC EDITING IN BREAST CANCER, G4834287653, Safeguarding honeybees: understanding host-parasite interactions at the level of proteins, ARC Training Centre for Personalised Therapeutics Technologies, Development of technologies to monitor multimolecular complexes, G6324380050, The molecular pharmacology of receptor complexes, Evolutionary proteomics of social insects, Linking evolutionary and molecular biology to safeguard Australian honeybees, G8812127397
OpenAlex ID: W3081723850