Baicalin Inhibits Lung Cancer Cell Proliferation and Migration via ALOX12-Mediated Ferroptosis.

Abstract

Background: Lung cancer remains a leading cause of cancer-related mortality worldwide, primarily due to late-stage diagnosis and resistance to conventional therapies. Recent studies have highlighted the potential of natural compounds in enhancing the efficacy and reducing the side effects of conventional cancer treatments. Baicalin, a bioactive compound from Scutellaria baicalensis, exhibits significant anticancer properties.

Objectives: This study aimed to investigate the role of baicalin in modulating lung cancer cell behavior through the arachidonate 12-lipoxygenase (ALOX12)-mediated ferroptosis pathway.

Methods: We employed cyber pharmacology and molecular docking techniques to predict and validate the interaction between baicalin and ALOX12. In vitro experiments were conducted on A549 lung cancer cells to assess the effects of baicalin on cell proliferation, migration, and invasion. The expression levels of ALOX12, reactive oxygen species (ROS), and ferroptosis markers, such as Glutathione Peroxidase 4 (GPX4) and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), were measured.

Results: Baicalin treatment significantly upregulated ALOX12 expression in lung cancer cells, and this upregulation was associated with a reduction in cell proliferation, migration, and invasion. Furthermore, baicalin-induced ferroptosis was characterized by increased ROS levels, iron accumulation, and elevated expression of GPX4 and ACSL4. These findings suggest that baicalin enhances ferroptosis through ALOX12 activation, synergistically inhibiting cancer cell growth.

Conclusion: Baicalin significantly upregulated ALOX12 expression, promoted ferroptosis, and inhibited the proliferation and migration of A549 lung cancer cells. This finding provides evidence for the potential use of baicalin as a therapeutic agent for lung cancer and highlights the importance of ALOX12 in lung cancer treatment strategies.