Figure 17. Targeting flavin-containing enzymes eradicates CSCs.

Flavins (FMN, FAD and Riboflavin) have been independently used as markers for high mitochondrial OXPHOS or increased CSC activity. However, it remained unknown whether flavins were selectively required for CSC propagation. Here, we showed that DPI, which is known to specifically target flavin-containing enzymes, behaves as a powerful mitochondrial OXPHOS inhibitor and successfully eradicates CSCs with high potency, in the low nano-molar range. Therefore, these findings provide the first proof-of-concept that inhibiting flavin-containing enzymes is a new viable strategy for effectively targeting CSCs.