Dithiiranylmethyloxy azaxanthone shows potent anti-tumor activity via suppression of HER2 expression and HER2-mediated signals in HER2-overexpressing breast cancer cells

Autor: Eunyoung Lee, Kyu Yeon Jun, Jung Min Nam, Youngjoo Kwon, Younghwa Na, Yeung Bae Jin, Hanbyeol Kwon, Yun Sil Lee, Kyung Hwa Jeon
Rok vydání: 2013
Předmět:
Human epidermal growth factor receptor 2
medicine.medical_specialty
Receptor
ErbB-2
Xanthones
Mice
Nude
Pharmaceutical Science
Antineoplastic Agents
Breast Neoplasms
Biology
Mice
chemistry.chemical_compound
Cell Line
Tumor
Neoplasms
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Humans
Potency
Epidermal growth factor receptor
skin and connective tissue diseases
Autocrine signalling
Cell Proliferation
ESX–Sur2 interaction inhibitor
Reporter gene
Mediator Complex
Proto-Oncogene Proteins c-ets
Canertinib
Cell growth
Cell Cycle
HEK 293 cells
Xenograft Model Antitumor Assays
Azaxanthone derivatives
Tumor Burden
DNA-Binding Proteins
Tamoxifen
HEK293 Cells
Tamoxifen resistant breast cancer
Endocrinology
chemistry
Cancer research
biology.protein
Female
Mitogen-Activated Protein Kinases
Signal Transduction
Transcription Factors
medicine.drug
Zdroj: European Journal of Pharmaceutical Sciences. 50:181-190
ISSN: 0928-0987
DOI: 10.1016/j.ejps.2013.06.014
Popis: Dithiiranylmethyloxy azaxanthone (CHO10), which was discovered by screening compounds in a reporter gene assay, inhibited the ESX–Sur2 interaction in a dose-dependent manner with potency similar to canertinib. The intervention of CHO10 during the ESX–Sur2 interaction caused down-regulation of both HER2 gene amplification and HER2 protein expression, which led to the attenuation of HER2-mediated downstream signal cascades and autocrine cell growth in SK-BR-3 cells, which are HER2 overexpressing breast cancer cells. The cell growth inhibitory activity of CHO10 was more potent in HER2-overexpressing breast cancer cells (AU-565, BT474 and SK-BR-3) than in HER2-negative cells (HEK293) and breast cancer cells (MCF-7) that express a basal level of HER2. Treatment with CHO10 in combination with tamoxifen sensitized BT474 cells, tamoxifen-resistant ER-positive breast cancer cell line, toward chemotherapeutic. The anti-tumor activity of CHO10 was validated by the significant reduction in tumor size of NCI-H460 or DLD-1 subcutaneously implanted xenograft tumors through treatment with 1mg/kg five times every other 2days.
Databáze: OpenAIRE
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