Related Experiment Video
Updated: Sep 20, 2025
A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
An FDA-approved drug library screening identifies proteasome inhibitors as selective cytotoxic agents for
Che-Yuan Hsu1,2, Teruki Yanagi3,4, Kodai Miyamoto1,2
1Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Abstract:
Cutaneous angiosarcoma (CAS) is a life-threatening neoplasm with a 5-year survival rate of under 40% in advanced cases. As available treatments for CAS are limited, novel therapeutics must be explored. To identify potential therapeutic candidates, we conducted a drug screening analysis using an angiosarcoma cell line, HAMON. Cancer-related gene analysis revealed alterations in FGFR4, MYCN, CDKN2A, NF1, TP53, KDM6A, ATRX, MSH6, ATM, and NOTCH1 in HAMON cells. Screening of 4681 FDA-approved drugs identified four candidate compounds, with the proteasome inhibitor bortezomib selected for further study. ATP and MTT assays revealed bortezomib to be the most effective candidate against HAMON cells. Clonogenic assays revealed fewer HAMON cell colonies in the range of 1-10 nM bortezomib. DNA-content fluorescence-activated cell sorting analysis revealed a notable increase in the sub-G0/G1 phases, suggesting cell death without cell cycle arrest. Annexin V-propidium iodide staining revealed a significant increase in the percentage of early and late apoptotic cells in the bortezomib group. Mechanistically, bortezomib induced activation of NF-κB and endoplasmic reticulum stress signaling. The administration of bortezomib to immunocompromised mice implanted with HAMON cells induced apoptosis of tumor cells. This study identified the proteasome inhibitor bortezomib as a potential candidate for angiosarcoma in vitro and in vivo.
Insights
The proteasome inhibitor bortezomib shows promise as a novel therapeutic for cutaneous angiosarcoma (CAS). This study identified bortezomib as effective in reducing CAS cell growth and inducing apoptosis in vitro and in vivo.
Area of Science:
- Oncology
- Drug Discovery
- Cancer Biology
Background:
- Cutaneous angiosarcoma (CAS) is an aggressive cancer with poor prognosis and limited treatment options.
- Identifying novel therapeutic strategies is crucial for improving patient outcomes in advanced CAS.
- Genetic analysis of CAS cell lines reveals potential therapeutic targets.
Purpose of the Study:
- To screen FDA-approved drugs for potential efficacy against cutaneous angiosarcoma.
- To identify and validate novel therapeutic candidates for CAS treatment.
- To investigate the mechanism of action of promising drug candidates.
Main Methods:
- Drug screening of 4681 FDA-approved compounds using the HAMON angiosarcoma cell line.
- In vitro assays including ATP, MTT, clonogenic, DNA-content FACS, and Annexin V-propidium iodide staining.
- In vivo studies using immunocompromised mice xenograft models.
Main Results:
- Bortezomib, a proteasome inhibitor, emerged as the most effective compound in drug screening.
- Bortezomib demonstrated significant anti-proliferative and pro-apoptotic effects on CAS cells in vitro.
- Bortezomib induced tumor cell apoptosis in vivo and activated NF-κB and endoplasmic reticulum stress pathways.
Conclusions:
- Bortezomib is identified as a potential therapeutic candidate for cutaneous angiosarcoma.
- The study provides evidence for bortezomib's efficacy in both in vitro and in vivo models of CAS.
- Further clinical investigation of bortezomib for CAS treatment is warranted.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...