Pharmacological intervention of Chinese medicine via regulating ferroptosis in gastric cancer

Gastric cancer (GC) is the second most frequently diagnosed malignancy, as well as the second most common cause of cancer-related deaths in China. Drug resistance is a major factor that limits the efficacy of GC chemotherapy. Given the increased resistance of GC cells to ferroptosis, activating the ferroptotic pathways has emerged as a promising therapeutic strategy against GC. This review summarizes the pathways involved in ferroptosis resistance in GC cells and the mechanisms underlying the therapeutic effects of herbal formulae and their bioactive compounds, with particular emphasis on ferroptosis. Multiple signaling pathways are implicated in regulating ferroptosis in GC cells, including the Wnt/β-catenin, PI3K/AKT/mTOR, TGF-β1/Smad, NF-κB, and Hippo pathways. According to previous clinical trials, traditional Chinese medicine (TCM) formulations can prolong the survival or increase survival chances in patients with GC, and reduce adverse reactions, thereby improving the quality of life. Finally, preclinical studies have shown TCMs and their bioactive compounds can ameliorate GC progression by triggering ferroptosis. Despite these beneficial effects on patients with GC, the underlying molecular mechanisms of TCM in GC have not been fully elucidated yet, and there are also some crucial shortcomings in the current studies. Therefore, further clinical trials and experimental studies are required to deepen our understanding of the mechanisms for activating ferroptosis in GC cells through TCM.