Journal article
The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells
American journal of cancer research, v 7(7), pp 1486-1500
01 Jul 2017
PMID: 28744399
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In breast cancer the use of small molecule inhibitors of tyrosine kinase activity of the ERBB family members improves survival thus represents a valuable therapeutic strategy. The addition of calcitriol, the most active metabolite of vitamin D, or some of its analogs, to conventional anticancer drugs, including tyrosine kinase inhibitors (TKIs), has shown an increased effect on the inhibition of cancer cell growth. In this work, we have evaluated the effects and the mechanism of action of the combination of calcitriol or its analog EB1089 with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell proliferation in a concentration-dependent manner. Addition of calcitriol or EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth and AKT and MAPK phosphorylation than all compounds alone. The combined treatments incremented also the expression of active caspase 3 and induced cell death in two and three-dimensional cell culture and significantly inhibited anchorage-independent colony formation. Our results suggest that the addition of calcitriol or its analog EB1089 to conventional targeted therapies, including lapatinib or neratinib might be of benefit to patients with breast cancer, particularly those with an EGFR and/or HER2 positive phenotype.
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Details
- Title
- The addition of calcitriol or its synthetic analog EB1089 to lapatinib and neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer cells
- Creators
- Mariana Segovia-Mendoza - Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránLorenza Díaz - Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránHeriberto Prado-Garcia - Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Mauricio J Reginato - Drexel UniversityFernando Larrea - Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránRocío García-Becerra - Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
- Publication Details
- American journal of cancer research, v 7(7), pp 1486-1500
- Publisher
- e-Century Publishing Corporation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000406665600007
- Other Identifier
- 991019168356904721
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- Collaboration types
- International collaboration
- Web of Science research areas
- Oncology