Dehydroascorbic Acid Induces Cell Death in Sarcoma Stem Cells Under bFGF-Mediated Stemness-Supporting Conditions.

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Biochemistry

Background:

• Sarcomas exhibit resilience and high metastatic potential, driven by cancer stem cells (CSCs).
• Ascorbic acid (AA) and dehydroascorbic acid (DHA) show potential for cancer cell targeting, but their effect on sarcoma CSCs is understudied.
• Recent findings suggest AA influences CSC characteristics and cytotoxicity.

Purpose of the Study:

• To investigate the sensitivity of sarcoma CSCs to ascorbate (AA and DHA).
• To evaluate the selective cytotoxic effects of DHA on sarcoma CSCs.
• To explore the influence of basic fibroblast growth factor (bFGF) on DHA's efficacy.

Main Methods:

• Isolation of CSCs from six sarcoma patient-derived samples using sphere assays.
• Evaluation of stem identity via gene expression profiling and dye-efflux assays.
• Cytotoxicity testing of AA and DHA, with and without bFGF, followed by gene expression analysis and mutation profiling.

Main Results:

• DHA demonstrated a selective cytotoxic effect on sarcoma CSCs.
• The presence of bFGF modulated DHA's cytotoxic impact.
• DHA, in conjunction with bFGF, significantly affected oxidative stress response and cellular metabolism in CSCs.
• Specific mutations in liposarcoma and rhabdomyosarcoma, when combined with bFGF and DHA, induced cell death rather than proliferation.

Conclusions:

• DHA is a promising agent for selectively targeting sarcoma CSCs.
• The combination of DHA and bFGF presents a potential therapeutic strategy for specific sarcomas by inducing cell death.
• Understanding CSC-specific vulnerabilities, like response to DHA and bFGF, is crucial for overcoming sarcoma therapy resistance.