Quantitative proteomic profiling reveals key pathways in the anti-cancer action of methoxychalcone derivatives in triple negative breast cancer
| Autor: | Sharon J. Pitteri, Meghan A. Rice, Sanjay V. Malhotra, Catherine C. Going, Vineet Kumar, Tanya Stoyanova, Mallesh Pandrala, Dhanir Tailor, Alisha M. Birk |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteomics Chalcone Quantitative proteomics Antineoplastic Agents Apoptosis Triple Negative Breast Neoplasms Tandem mass tag Biochemistry Article Metastasis Flow cytometry Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Humans Triple-negative breast cancer Cell Proliferation medicine.diagnostic_test Chemistry General Chemistry medicine.disease G1 Phase Cell Cycle Checkpoints 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research Female Metabolic Networks and Pathways |
| Zdroj: | J Proteome Res |
| Popis: | Triple negative breast cancer is an aggressive, heterogeneous disease with high recurrence and metastasis rates even with modern chemotherapy regimens and thus is in need of new therapeutics. Here, three novel synthetic analogues of chalcones, plant-based molecules that have demonstrated potency against a wide variety of cancers, were investigated as potential therapeutics for triple negative breast cancer. These compounds exhibit IC(50) values of ~ 5 μM in triple negative breast cancer cell lines and are more potent against triple negative breast cancer cell lines than against non-tumor breast cell lines according to viability experiments. Tandem mass tag-based quantitative proteomics followed by gene set enrichment analysis and validation experiments using flow cytometry, apoptosis, and western blot assays revealed three different anti-cancer mechanisms for these compounds. First, the chalcone analogues induce the unfolded protein response followed by apoptosis. Second, increases in the abundances of MHC-I pathway proteins occurs, which would likely result in immune stimulation in an organism. And third, treatment with the chalcone analogues causes disruption of the cell cycle by interfering with microtubule structure and by inducing G1 phase arrest. These data demonstrate the potential of these novel chalcone derivatives as treatments for triple negative breast cancer, though further work evaluating their efficacy in vivo is needed. |
| Databáze: | OpenAIRE |
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