Epigenetic anticancer agents cause HMGB1 release in vivo

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• High mobility group box 1 (HMGB1) is a nuclear protein involved in cellular stress responses and immune modulation.
• Elevated extracellular HMGB1 is associated with immunogenic cell death (ICD) and can stimulate anti-tumor immunity.
• Identifying novel anticancer agents that induce HMGB1 release is crucial for developing new cancer therapies.

Purpose of the Study:

• To systematically search for and identify anticancer agents that promote the release of HMGB1 from cells.
• To investigate the potential of identified agents to increase plasma HMGB1 levels in vivo.
• To explore the mechanisms by which these agents induce HMGB1 release, focusing on ICD and epigenetic modification.

Main Methods:

• Systematic literature search for anticancer drugs with HMGB1-releasing properties.
• In vivo studies in mice to measure plasma HMGB1 levels after drug administration.
• Classification of identified agents based on their known mechanisms of action (e.g., ICD inducers, epigenetic modifiers).

Main Results:

• Several anticancer agents were identified that effectively increase extracellular HMGB1 levels.
• Oxaliplatin, a known immunogenic cell death inducer, was confirmed to elevate plasma HMGB1.
• Epigenetic modifiers, including azacitidine, decitabine, and suberoylanilide hydroxamic acid (SAHA), also demonstrated the ability to increase HMGB1 levels in vivo.

Conclusions:

• Anticancer agents, including chemotherapy drugs and epigenetic modifiers, can induce the release of HMGB1.
• These findings highlight a potential mechanism for enhancing anti-tumor immunity through HMGB1-mediated pathways.
• The identified drugs represent promising candidates for further investigation in cancer immunotherapy.