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Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
by
Iyer, K. Swaminathan
, Sorolla, Anabel
, Ho, Diwei
, Golden, Emily
, Davern, Kathleen
, Johnstone, Elizabeth
, Pfleger, Kevin
, Blancafort, Pilar
, Woodward, Eleanor
, Wang, Edina
, Redfern, Andrew
, Duffy, Ciara
, Baer, Boris
in
631/67/1347
/ 692/4017
/ 692/4028/67/1347
/ Bees
/ Biological products
/ Breast cancer
/ Cancer Research
/ Disease prevention
/ Gene Therapy
/ Human Genetics
/ Internal Medicine
/ Medicine
/ Medicine & Public Health
/ Oncology
/ Venom
2020
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Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
by
Iyer, K. Swaminathan
, Sorolla, Anabel
, Ho, Diwei
, Golden, Emily
, Davern, Kathleen
, Johnstone, Elizabeth
, Pfleger, Kevin
, Blancafort, Pilar
, Woodward, Eleanor
, Wang, Edina
, Redfern, Andrew
, Duffy, Ciara
, Baer, Boris
in
631/67/1347
/ 692/4017
/ 692/4028/67/1347
/ Bees
/ Biological products
/ Breast cancer
/ Cancer Research
/ Disease prevention
/ Gene Therapy
/ Human Genetics
/ Internal Medicine
/ Medicine
/ Medicine & Public Health
/ Oncology
/ Venom
2020
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Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
by
Iyer, K. Swaminathan
, Sorolla, Anabel
, Ho, Diwei
, Golden, Emily
, Davern, Kathleen
, Johnstone, Elizabeth
, Pfleger, Kevin
, Blancafort, Pilar
, Woodward, Eleanor
, Wang, Edina
, Redfern, Andrew
, Duffy, Ciara
, Baer, Boris
in
631/67/1347
/ 692/4017
/ 692/4028/67/1347
/ Bees
/ Biological products
/ Breast cancer
/ Cancer Research
/ Disease prevention
/ Gene Therapy
/ Human Genetics
/ Internal Medicine
/ Medicine
/ Medicine & Public Health
/ Oncology
/ Venom
2020
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Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
Journal Article
Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer
2020
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Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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