{"id":157780,"date":"2023-02-12T02:22:20","date_gmt":"2023-02-12T08:22:20","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2023\/02\/honeybee-venom-and-melittin-suppress-growth-factor-receptor-activation-in-her2-enriched-and-triple-negative-breast-cancer"},"modified":"2023-02-12T02:22:20","modified_gmt":"2023-02-12T08:22:20","slug":"honeybee-venom-and-melittin-suppress-growth-factor-receptor-activation-in-her2-enriched-and-triple-negative-breast-cancer","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2023\/02\/honeybee-venom-and-melittin-suppress-growth-factor-receptor-activation-in-her2-enriched-and-triple-negative-breast-cancer","title":{"rendered":"Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer"},"content":{"rendered":"<p style=\"padding-right: 20px\"><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/honeybee-venom-and-melittin-suppress-growth-factor-receptor-activation-in-her2-enriched-and-triple-negative-breast-cancer.jpg\"><\/a><\/p>\n<p>Apitherapy is an emerging field with the potential to impact the economic aspects of cancer research globally, particularly in under-resourced communities. To date, however, studies are yet to fully investigate the molecular mechanism of action of honeybee venom and melittin, and their consequent optimum usage in the oncology arena is yet to be comprehensively investigated, particularly for the treatment of breast cancer, the most commonly occurring cancer in women worldwide<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\" title=\"Fitzmaurice, C. et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 Cancer Groups, 1990 to 2015. JAMA Oncol. 3,524 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR2\" id=\"ref-link-section-d222357718e2334\">2<\/a><\/sup>. TNBCs and HER2-enriched tumors are highly aggressive breast cancer subtypes. TNBC is associated with the highest mortality and, despite frequent EGFR expression, commonly displays resistance to anti-EGFR therapies with high dependence on PI3K\/Akt signaling for proliferation, survival, and chemotherapy resistance<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 34\" title=\"Shah, S. P. et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486395&ndash;399 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR34\" id=\"ref-link-section-d222357718e2338\">34<\/a><\/sup>.<\/p>\n<p>Anti-HER2 therapies have substantially improved long-term survival in early-stage HER2-positive cancers, but the majority of late-stage patients eventually develop resistance and succumb to the disease<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 33\" title=\"Gagliato, D. de M., Jardim, D. L. F., Marchesi, M. S. P. & Hortobagyi, G. N. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget 7, 64431&ndash;64446 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR33\" id=\"ref-link-section-d222357718e2345\">33<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 35\" title=\"Costa, R. et al. Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: new discoveries and practical insights for drug development. Cancer Treat. Rev. 53111&ndash;119 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR35\" id=\"ref-link-section-d222357718e2348\">35<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 36\" title=\"Swain, S. M. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N. Engl. J. Med. 372724&ndash;734 (2015).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR36\" id=\"ref-link-section-d222357718e2351\">36<\/a><\/sup>. Not only did we demonstrate selectivity of honeybee venom and melittin for malignant cells, but we also revealed higher potencies for these aggressive types of breast cancer.<\/p>\n<p>Here, we show that honeybee venom and melittin suppress the ligand-induced phosphorylation of EGFR and HER2, dynamically modulating downstream signaling pathways in breast cancer cells. We propose that melittin directly or indirectly inhibits RTK dimerization. Melittin may also enter the cell to directly or indirectly modulate downstream signaling pathways<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 25\" title=\"Kohno, M., Horibe, T., Ohara, K., Ito, S. & Kawakami, K. The membrane-lytic peptides K8L9 and melittin enter cancer cells via receptor endocytosis following subcytotoxic exposure. Chem. Biol. 21, 1&ndash;11 (2014).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR25\" id=\"ref-link-section-d222357718e2358\">25<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 60\" title=\"Sharma, S. V. Melittin resistance: a counterselection for ras transformation. Oncogene 7193&ndash;201 (1992).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR60\" id=\"ref-link-section-d222357718e2361\">60<\/a><\/sup>. Previous work has shown that melittin can be targeted to HER2-overexpressing cell lines using immunoliposomes bearing trastuzumab<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 61\" title=\"Barraj\u00f3n-Catal\u00e1n, E. et al. Selective death of human breast cancer cells by lytic immunoliposomes: correlation with their HER2 expression level. Cancer Lett. 290192&ndash;203 (2010).\" href=\"https:\/\/www.nature.com\/articles\/s41698-020-00129-0#ref-CR61\" id=\"ref-link-section-d222357718e2365\">61<\/a><\/sup>. Here, we demonstrate that melittin alone selectively targets HER2-and EGFR-overexpressing breast cancer cells. Interestingly, melittin was more potently toxic to breast cancer cells compared to honeybee venom, warranting further investigation.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Apitherapy is an emerging field with the potential to impact the economic aspects of cancer research globally, particularly in under-resourced communities. To date, however, studies are yet to fully investigate the molecular mechanism of action of honeybee venom and melittin, and their consequent optimum usage in the oncology arena is yet to be comprehensively investigated, [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,39],"tags":[],"class_list":["post-157780","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-economics"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/157780","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=157780"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/157780\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=157780"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=157780"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=157780"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}