Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
| Autor: | Diwei Ho, Kevin D. G. Pfleger, Kathleen Davern, Pilar Blancafort, Emily Golden, K. Swaminathan Iyer, Anabel Sorolla, Ciara Duffy, Elizabeth K. M. Johnstone, Andrew Redfern, Boris Baer, Edina Wang, Eleanor A. Woodward |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Venom complex mixtures lcsh:RC254-282 Melittin Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Growth factor receptor Receptor Triple-negative breast cancer Cancer 030304 developmental biology RGD motif 0303 health sciences Molecular medicine technology industry and agriculture lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncology chemistry Cell culture 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | NPJ precision oncology, vol 4, iss 1 npj Precision Oncology, Vol 4, Iss 1, Pp 1-16 (2020) NPJ Precision Oncology |
| Popis: | Despite decades of study, the molecular mechanisms and selectivity of the biomolecular components of honeybee (Apis mellifera) 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. |
| Databáze: | OpenAIRE |
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