Rotundifuran (RF), a potent anti-inflammatory and anti-cancer compound, is a natural compound predominantly present in Vitex Rotundifolia. Herein, we investigated the effects of RF on the growth of lung cancer cells. Our findings suggested that RF inhibits cell growth, highlighting its potential as a therapeutic agent for cancer treatment. Interestingly, we observed that cell growth inhibition was not due to apoptosis, as caspases were not activated and DNA fragmentation did not occur. Furthermore, we found that intracellular vacuoles and autophagy were induced, but RF-induced cell death was not affected when autophagy was inhibited. This prompted us to investigate other possible mechanisms underlying cell growth inhibition. Through a cDNA chip analysis, we confirmed changes in the expression of ferroptosis-related genes and observed lipid peroxidation. We further examined the effect of ferroptosis inhibitors and found that they alleviated cell growth inhibition induced by RF. We also observed the involvement of calcium signaling, ROS accumulation, and JNK signaling in the induction of ferroptosis. Our findings suggested that RF is a potent anti-cancer drug and further studies are needed to validate its clinal use.

中文翻译：

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Rotundifuran 诱导肺癌细胞铁死亡和线粒体通透性转变


Rotundifuran (RF) 是一种有效的抗炎和抗癌化合物，是主要存在于 Vitex Rotundifolia 中的天然化合物。在此，我们研究了射频对肺癌细胞生长的影响。我们的研究结果表明射频抑制细胞生长，凸显了其作为癌症治疗药物的潜力。有趣的是，我们观察到细胞生长抑制并不是由于细胞凋亡，因为半胱天冬酶没有被激活，DNA 断裂也没有发生。此外，我们发现细胞内空泡和自噬被诱导，但当自噬被抑制时，射频诱导的细胞死亡不受影响。这促使我们研究细胞生长抑制的其他可能机制。通过cDNA芯片分析，我们确认了铁死亡相关基因表达的变化，并观察到脂质过氧化。我们进一步检查了铁死亡抑制剂的作用，发现它们减轻了 RF 引起的细胞生长抑制。我们还观察到钙信号、ROS 积累和 JNK 信号在铁死亡诱导中的参与。我们的研究结果表明 RF 是一种有效的抗癌药物，需要进一步研究来验证其临床用途。