Self-assembling peptides induced by eyes absent enzyme to boost the efficacy of doxorubicin therapy in drug-resistant breast cancer cells

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dc.creatorCarney, Emily
dc.creatorGhasem Zadeh Moslabeh, Forough
dc.creatorKang, Soo-Yeon
dc.creatorBunnell, Bruce A.
dc.creatorLee, Moo-Yeal
dc.creatorHabibi, Neda
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2024-08-08T19:50:02Z
dc.date.available2024-08-08T19:50:02Z
dc.date.issued2024-06-25
dc.description.abstractEnzyme-induced self-assembly (EISA) is a recently developed nanotechnology technique in which small molecules are induced by cellular enzymes self-assembling into nanostructures inside cancer cells. This technique can boost the efficacy of chemotherapy drugs by avoiding drug efflux, inhibiting the cells' DNA repair mechanisms, and targeting the mitochondria. In this work, we study the self-assembly of a short peptide and its fluorescence analogue induced by Eyes absent (EYA) tyrosine phosphatases to boost the efficacy of doxorubicin (DOX) therapy in drug-resistant types of breast cancer cells, MDA-MB-231 and MCF-7. The peptides Fmoc-FF-YP and NBD-FF-YP were synthesized with the solid-phase peptide synthesis (SPPS) method and analyzed with HPLC and MALDI-TOF. Dynamic light scattering was used to determine the size distribution of peptides exposed to the EYA enzyme in vitro. The presence of EYA enzymes in breast cancer cells was confirmed using the western blotting assay. The intracellular location of the peptide self-assembly was studied by imaging fluorescence NBD-tagged peptides. The efficacy of the peptide alone and with DOX was determined against MCF-7 and MDA-MB-231 using MTT and LIVE-DEAD assays. Nucleus and cytoplasm F-actin (Phalloidin) staining was used to determine cell morphology changes in response to the combination therapy of peptides/DOX. At an optimal concentration, the peptides are not toxic to the cells; however, they boost the efficacy of DOX against drug-resistant breast cancer cells. We used state-of-the-art computer-aided techniques to predict the molecular structure of peptides and their interactions with EYA. This study demonstrates an approach for incorporating non-cytotoxic components into DOX combination therapy, thereby avoiding increased systemic burden or adverse effects.
dc.description.sponsorshipResearch reported in this publication was supported by the National Institute of General Medical Science (NIGMS) of the National Institutes of Health (NIH), United States, under award number R16GM150848.
dc.identifier.citationCarney, E., Ghasem Zadeh Moslabeh, F., Kang, S. Y., Bunnell, B. A., Lee, M. Y., & Habibi, N. (2024). Self-assembling peptides induced by eyes absent enzyme to boost the efficacy of doxorubicin therapy in drug-resistant breast cancer cells. Heliyon, 10(13), e33629. https://doi.org/10.1016/j.heliyon.2024.e33629
dc.identifier.issn2405-8440
dc.identifier.issue13
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32889
dc.identifier.volume10
dc.publisherElsevier B.V.
dc.relation.urihttps://doi.org/10.1016/j.heliyon.2024.e33629
dc.rights.holder© 2024 The Authors.
dc.rights.licenseAttribution-Noncommercial 4.0 International (CC BY-NC 4.0 Deed)
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceHeliyon
dc.subjectbreast cancer
dc.subjectenzyme
dc.subjectpeptide
dc.subjectself-assembly
dc.titleSelf-assembling peptides induced by eyes absent enzyme to boost the efficacy of doxorubicin therapy in drug-resistant breast cancer cells
dc.typeArticle
dc.type.materialtext

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