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<p>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 <i>Curcuma longa</i> 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 <b>(</b>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月5日

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  • Nurdan Sena Degirmenci,
  • Zarife Yildirim,
  • Gamze Padar,
  • Fikrettin Sahin,
  • Zehra Omeroglu Ulu

摘要

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.