Curcumin potentiates rhabdomyosarcoma radiosensitivity by suppressing NF-κB activity

Area of Science:

• Oncology
• Radiation Oncology
• Molecular Biology

Background:

• Ionizing radiation (IR) is crucial for alveolar rhabdomyosarcoma (ARMS) treatment.
• Nuclear Factor-kappaB (NF-κB) activation by IR is linked to cancer radioresistance.
• Targeting NF-κB may improve IR efficacy in ARMS.

Purpose of the Study:

• To evaluate curcumin and genetic inhibitors of NF-κB as radiosensitizers for ARMS.
• To investigate the role of NF-κB pathways in IR-induced radioresistance in ARMS.
• To assess the therapeutic potential of combining curcumin with IR against ARMS xenografts.

Main Methods:

• ARMS cells and xenografts were treated with IR, curcumin, or genetic NF-κB inhibitors (SR-IκBα, SR-p100).
• NF-κB activity, target protein expression, tumor proliferation, apoptosis, and endothelial cell count were assessed.
• In vivo synergistic antitumor activity was evaluated in mouse xenograft models.

Main Results:

• IR upregulated NF-κB activity and target proteins in ARMS cells.
• Curcumin inhibited radiation-induced NF-κB activation and potentiated IR's antitumor effects.
• Combination therapy with curcumin and IR demonstrated synergistic activity, reducing proliferation and increasing apoptosis in xenografts.
• Genetic inhibition of the classical NF-κB pathway (SR-IκBα) increased IR sensitivity, while the alternative pathway inhibitor (SR-p100) did not.

Conclusions:

• Curcumin acts as a radiosensitizer for ARMS by suppressing the classical NF-κB pathway activated by IR.
• Combination therapy of curcumin and IR shows significant antitumor efficacy in ARMS models.
• These findings support the clinical investigation of curcumin as a radiosensitizer for alveolar rhabdomyosarcoma treatment.