Investigating the interaction between calcium signaling and ferroptosis for novel cancer treatment.

BACKGROUND

Drug resistance in cancer is steadily rising, making the development of new therapeutic targets increasingly critical for improving treatment outcomes.

PURPOSE: The mutual regulation of ions is essential for cell growth. Based on this concept, ion interference strategies offer a highly effective approach for cancer treatment. Calcium ions (Ca2+), as major second messengers, are closely associated with ion exchange and homeostasis. Disruptions in this balance can lead to cell death. However, while iron ions are also crucial, the connection between Ca2+and iron-induced cell death (ferroptosis) has not been well established. Therefore, this study suggests that Ca2+ may play a role in the induction of ferroptosis, presenting a novel and efficient target for cancer therapy.

STUDY

DESIGN

PubMed, Google Scholar, and Web of Science databases were systematically searched for articles published in the past 15 years on the mechanisms of calcium ion-induced ferroptosis in cancer and related drugs.

RESULTS

The analysis highlights how Ca2+regulate ferroptosis. The mechanisms by which Ca2+influence ferroptosis are summarized based on existing literature, and relevant drugs that act on Ca2+/ferroptosis axis are outlined.

CONCLUSION

Ca2+ regulate ferroptosis primarily through the modulation of reactive oxygen species (ROS) and glutathione (GSH) levels, a mechanism that applies to a wide range of cancer cells as well as paracancerous and normal cells in cancer treatment. Furthermore, plant-derived active compounds exhibit potent anticancer properties and often act on the Ca2+/ferroptosis axis. These natural compounds could play a significant role in the development of new cancer treatment strategies.