Chen Pei, Yang Jin, Chen Lin, Liu Chenhuan, Li Zhihao, Long Xiaoming, Wu Jinbang, Wu Bo, Wu Jianjun
Department of Urology, Zunyi Medical University, Zunyi, Guizhou, China.
Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China.
Chem Biol Drug Des. 2025 Mar;105(3):e70071. doi: 10.1111/cbdd.70071.
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 Fe, 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.
毛兰素是一种从铁皮石斛中提取的联苯化合物，具有显著的抗肿瘤活性。然而，毛兰素在透明细胞肾细胞癌（ccRCC）中的具体作用及其潜在分子机制尚未得到充分研究。本研究旨在通过一系列实验证明毛兰素能有效抑制ccRCC的增殖和迁移并诱导其凋亡过程，从而填补这一空白。更重要的是，我们发现毛兰素还能引发ccRCC中的铁死亡，这一过程伴随着铁、丙二醛（一种脂质过氧化产物）和活性氧（ROS）水平的显著升高，以及线粒体膜电位和谷胱甘肽（GSH）水平的降低。这些变化强烈表明毛兰素在诱导铁死亡中起关键作用。为进一步探究其潜在机制，我们推测毛兰素可能抑制JAK-STAT信号通路的磷酸化水平，从而阻断铁死亡信号通路中关键蛋白SLC7A11的功能，促进铁死亡的发生。这一发现不仅揭示了毛兰素治疗ccRCC的新机制，也为未来相关药物的研发提供了新思路。总之，基于毛兰素可诱导ccRCC发生铁死亡这一重要发现，我们有理由相信毛兰素有望成为治疗ccRCC的新型药物。
