Combination of sodium pentaborate pentahydrate, curcumin and piperine treatment induces ferroptosis in hepatocellular carcinoma cells by regulating iron homeostasis and ROS activity in vitro.

Hepatocellular carcinoma (HCC) is one of the most prevalent solid cancers with the highest mortality rate, despite various treatment modalities. Sodium pentaborate pentahydrate (NaB) is a boron derivative that has an effect on cell death pathways against cancer. Curcumin (Cur) is the primary bioactive substance in the plant Curcuma longa and has anti-inflammatory, antioxidant and anti-cancer activities, mostly whose bioactivity is enhanced by combining piperine (Pip). Ferroptosis is a form of cell death different from apoptosis, necrosis, and autophagy due to reactive oxygen species (ROS) and disturbance in iron homeostasis. In our current study, we evaluated the effects of a NaB, Cur, and Pip combination on ferroptosis in HCC cell lines HepG2 and Hep3B. Our findings demonstrated that this combination treatment significantly decreased glutathione peroxidase (GSH-Px) activity and also increased ROS levels and intracellular ferrous iron in HCC cells. Additionally, qRT-PCR and Western blot analyses revealed upregulation of ferroptosis-related genes and protein expressions, indicating a synergistic induction of ferroptotic pathways by NaB, Cur, and Pip. These results suggest that this combination may represent a promising strategy for inducing ferroptosis in HCC, providing a basis for preliminary research into its potential as a therapeutic approach.