DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines
| العنوان: | DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines |
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| المؤلفون: | Filippo de Braud, Claudio Vernieri, Alessandra Gambacurta, Silvia D'Amico, Silvia Baldari, Gabriele Toietta, Francesca Bernassola, Flavio Di Giacinto, Ewa K. Krasnowska, Isabella Manni, Marco Ranalli, Maria Lucibello, Giulia Piaggio |
| المصدر: | Cells 9 (2020). doi:10.3390/cells9051260 info:cnr-pdr/source/autori:Silvia D'Amico .; Ewa Krystyna Krasnowska .; Isabella Manni I.; Gabriela Toietta .; Silvia Baldari .; Giulia Piaggio G.; Marco Ranalli ; Alesandra Gambacurta ; Claudio Vernieri ; Flavio Di Giacinto .; Francesca Bernassola .; Filippo de Braud ; Maria Lucibello ./titolo:DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines/doi:10.3390%2Fcells9051260/rivista:Cells/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:9 Cells Volume 9 Issue 5 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Receptor, ErbB-2, T-DM1, medicine.medical_treatment, Apoptosis, Mice, SCID, Microtubules, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Trastuzumab, Cytotoxic T cell, Epidermal growth factor receptor, Phosphorylation, skin and connective tissue diseases, biology, Settore BIO/11, Tumor Protein, Translationally-Controlled 1, General Medicine, Artemisinins, DHA, Female, Signal Transduction, medicine.drug, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, phospho-TCTP, Mitosis, Breast Neoplasms, Article, Breast cancer, Cell Line, Tumor, Biomarkers, Tumor, medicine, Animals, Humans, HER2-positive breast cancer, Cell Proliferation, Chemotherapy, business.industry, medicine.disease, Oxidative Stress, chemistry, Drug Resistance, Neoplasm, Trastuzumab emtansine, biology.protein, Cancer research, Translationally controlled tumour protein, Reactive Oxygen Species, business, Proto-Oncogene Proteins c-akt, DNA Damage |
| الوصف: | Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy. Increased levels of the phosphorylated form of Translationally Controlled Tumour Protein (phospho-TCTP) have been shown to be associated with a poor clinical response to trastuzumab therapy in HER2-positive breast cancer. Here we show that phospho-TCTP is essential for correct mitosis in human mammary epithelial cells. Reduction of phospho-TCTP levels by dihydroartemisinin (DHA) causes mitotic aberration and increases microtubule density in the trastuzumab-resistant breast cancer cells HCC1954 and HCC1569. Combinatorial studies show that T-DM1 when combined with DHA is more effective in killing breast cells compared to the effect induced by any single agent. In an orthotopic breast cancer xenograft model (HCC1954), the growth of the tumour cells resumes after having achieved a complete response to T-DM1 treatment. Conversely, DHA and T-DM1 treatment induces a severe and irreversible cytotoxic effect, even after treatment interruption, thus, improving the long-term efficacy of T-DM1. These results suggest that DHA increases the effect of T-DM1 as poison for microtubules and supports the clinical development of the combination of DHA and T-DM1 for the treatment of aggressive HER2-overexpressing breast cancer. |
| وصف الملف: | application/pdf |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50d87d8b3dbe15279ffc19762694738eTest https://doi.org/10.3390/cells9051260Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....50d87d8b3dbe15279ffc19762694738e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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