The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma

Area of Science:

• Hematology
• Oncology
• Natural Products Chemistry

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by frequent relapses.
• Current preclinical models inadequately address cancer stem cells (CSCs), which are implicated in MM relapse.
• Nuclear factor κB (NFκB) signaling is a key pathway in MM pathogenesis and survival.

Purpose of the Study:

• To investigate the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product NFκB inhibitors: parthenolide and andrographolide.
• To evaluate the efficacy of these agents in a three-dimensional bone marrow model that mimics the tumor microenvironment.

Main Methods:

• Utilized a three-dimensional tissue culture system with extracellular matrix to reconstruct human bone marrow.
• Tested the anti-MM-CSC activity of parthenolide and andrographolide.
• Assessed the impact of the bone marrow stromal compartment on the efficacy of the natural products.

Main Results:

• Parthenolide and andrographolide demonstrated potent anti-MM-CSC activity.
• Both agents exhibited preferential toxicity toward MM-CSCs compared to non-tumorigenic MM cells.
• The bone marrow stromal compartment abrogated andrographolide's activity but did not affect parthenolide's cytotoxicity.

Conclusions:

• Parthenolide and andrographolide are effective natural product inhibitors of MM-CSCs.
• Parthenolide exhibits anti-CSC activity independent of the bone marrow stromal compartment, suggesting broader therapeutic potential.
• These findings present a novel therapeutic strategy targeting MM-CSCs to potentially improve patient survival by preventing relapse.