Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Pharmacology

Background:

• Pancreatic tumors contain cancer stem cells (CSCs) driving metastasis and treatment resistance.
• Sorafenib (SO), a multikinase inhibitor, shows potential against solid tumors but can activate survival pathways.
• NF-kappaB activation by SO promotes CSC survival and tumor regrowth.

Purpose of the Study:

• To investigate the efficacy of SO in targeting pancreatic CSCs.
• To develop a strategy to enhance SO's CSC-targeting effects.
• To evaluate the combination of SO with sulforaphane (SF) for pancreatic CSC elimination.

Main Methods:

• Pancreatic cancer cells were treated with SO alone and in combination with SF.
• Assays included clonogenicity, spheroid formation, ALDH1 activity, in vivo tumor growth, proliferation, angiogenesis, apoptosis, and NF-kappaB activation.
• Combination therapy effects on CSC markers and epithelial-mesenchymal transition (EMT) proteins were analyzed.

Main Results:

• SO alone reduced CSC characteristics but induced NF-kappaB activation, promoting survival.
• SF eradicated SO-induced NF-kappaB binding, abrogating CSC properties and inducing apoptosis.
• Combination therapy synergistically reduced tumor size in vivo via apoptosis, reduced proliferation and angiogenesis, and downregulated EMT markers.

Conclusions:

• SF enhances SO's ability to eliminate pancreatic CSCs by inhibiting NF-kappaB.
• Combination therapy offers a promising strategy to overcome SO resistance and improve pancreatic cancer treatment.
• SF may be a valuable agent to potentiate SO therapy against CSCs in solid tumors.