Moscatilin Induces Ferroptosis in Clear Cell Renal Cell Carcinoma via the JAK–STAT Signaling Pathway

Abstract

Moscatilin, a biphenyl compound derived from Dendrobium nobile, exhibits significant anti-tumor activity. However, the specific role of moscatilin in clear cell renal cell carcinoma (ccRCC) and its underlying molecular mechanisms have not been fully studied. This study aims to fill this gap by demonstrating through a series of experiments that moscatilin can effectively inhibit the proliferation and migration of ccRCC and induce its apoptosis process. More importantly, we found that moscatilin can also trigger ferroptosis in ccRCC, a process accompanied by significant increases in Fe²⁺, MDA (a lipid peroxidation product), and ROS (reactive oxygen species) levels, as well as decreases in mitochondrial membrane potential and GSH (glutathione) levels. These changes strongly suggest a key role for moscatilin in inducing ferroptosis. To further explore its underlying mechanism, we speculate that moscatilin may inhibit the phosphorylation level of the JAK–STAT signaling pathway, thereby blocking the function of the key protein SLC7A11 in the ferroptosis signaling pathway, which promotes the occurrence of ferroptosis. This discovery not only reveals a new mechanism of moscatilin in the treatment of ccRCC but also provides new ideas for the development of related drugs in the future. In summary, based on the important discovery that moscatilin can induce ferroptosis in ccRCC, we have reason to believe that moscatilin has the potential to become a new type of drug for the treatment of ccRCC.