ArticleCancer chemotherapy and pharmacology2010
Targeted proteasome inhibition by Velcade induces apoptosis in human mesothelioma and breast cancer cell lines.
Article in Cancer chemotherapy and pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 40 citations in OpenAlex.
- Exploring the time-dependent regulatory potential of microRNAs in breast cancer cells treated with proteasome inhibitors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Antitumoral effects of Bortezomib in malignant mesothelioma: evidence of mild endoplasmic reticulum stress in vitro and activation of T cell response in vivo.Biology direct · 2023Article
- Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.Scientific reports · 2021Article
- Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.Frontiers in oncology · 2021Review
- Present and Future Prospect of Small Molecule & Related Targeted Therapy Against Human Cancer.Vivechan international journal of research · 2018Article
- Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.Scientific reports · 2017Article
- Novel systemic therapy against malignant pleural mesothelioma.Translational lung cancer research · 2017Review
- Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.PloS one · 2014Article
- Proteasomal regulation of caspase-8 in cancer cell apoptosis.Apoptosis : an international journal on programmed cell death · 2013Article
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- Therapeutic targeting of cancer cell cycle using proteasome inhibitors.Cell division · 2012Article
- Combined inhibition of cellular pathways as a future therapeutic option in fatal anaplastic thyroid cancer.Endocrine · 2012Article
- Article
- Antagonists of anaphase-promoting complex (APC)-2-cell cycle and apoptosis regulatory protein (CARP)-1 interaction are novel regulators of cell growth and apoptosis.The Journal of biological chemistry · 2011Article
- Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.Molecular and cellular biochemistry · 2011Article
- New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.PloS one · 2011Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
introductionThoracic malignancies and human breast cancer (HBC) continue to be aggressive solid tumors that are poor responders to the existing conventional standard chemotherapeutic approaches. Malignant pleural mesothelioma (MPM) is an asbestos-related tumor of the thoracic pleura that lacks effective treatment options. Altered ubiquitin proteasome pathway is frequently encountered in many malignancies including HBC and MPM and thus serves as an important target for therapeutic intervention strategies. Although proteasome inhibitor Velcade (Bortezomib) has been under clinical investigation for a number of cancers, limited preclinical studies with this agent have thus far been conducted in HBC and MPM malignancies. PURPOSE: To study the biological and molecular responses of MPM and HBC cells to Velcade treatments, and to identify mechanisms involved in transducing growth inhibitory effects of this agent.
methodsFlow-cytometric analyses coupled with western immunoblotting and gene-array methodologies were utilized to determine mechanisms of Velcade-dependent growth suppression of five MPM (H2595, H2373, H2452, H2461, and H2714) and two breast cancer (MDA MB-468, SKBR-3) cell lines.
resultsOur data revealed significant reduction in cell growth properties that were dose and time dependent. Velcade treatment resulted in G2M phase arrest, increased expression of cyclin-dependent kinase inhibitor p21 and pro-apoptotic protein Bax. Pretreatment of mesothelioma cells with Velcade showed synergistic effect with cisplatin combination regimens. High-throughput gene expression profiling among Velcade treated and untreated mesothelioma cell lines resulted in identification of novel transducers of apoptosis such as CARP-1, XAF1, and Troy proteins.
conclusionsVelcade targets cell cycle and apoptosis signaling to suppress MPM and HBC growth in part by activating novel transducers of apoptosis. This pilot study has paved way for further in-depth analysis of the downstream target molecules associated with presensitization of mesothelioma cells in finding effective therapeutic treatment options for both mesothelioma and recalcitrant breast cancers.
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