Crotoxin promotes macrophage reprogramming towards an antiangiogenic phenotype

Area of Science:

• Toxicology
• Cancer Biology
• Immunology

Background:

• Crotoxin (CTX), the main toxin in South American rattlesnake venom, exhibits anti-tumor properties.
• Tumor growth and progression are critically dependent on angiogenesis, the formation of new blood vessels.
• Macrophage secretory activity plays a crucial role in regulating angiogenesis.

Purpose of the Study:

• To investigate the effect of CTX on macrophage secretory activity in relation to angiogenesis.
• To determine if CTX can reprogram macrophages towards an anti-angiogenic phenotype.

Main Methods:

• In vitro study using thymic endothelial cells (EC) and macrophages.
• Macrophages were treated with CTX or supernatants from CTX-treated macrophages.
• Assessed EC proliferation, migration, adhesion, capillary-like tube formation, and levels of MMP-2, VEGF, and TNF-α.

Main Results:

• CTX-treated macrophages and their supernatants inhibited EC proliferation, adhesion, and migration.
• Capillary-like tube formation was significantly decreased in the presence of CTX-treated macrophages.
• Levels of angiogenic mediators (MMP-2, VEGF, TNF-α) were reduced in the supernatant of CTX-treated macrophages.

Conclusions:

• CTX induces a reprogramming of macrophages towards an anti-angiogenic phenotype.
• This macrophage reprogramming by CTX inhibits key processes of angiogenesis.
• CTX demonstrates potential as an anti-angiogenic agent for cancer therapy.