铁死亡已成为增强癌症治疗中化疗疗效的潜在机制。通过抑制核因子红细胞 2 相关因子 2 (Nrf2)，癌细胞可能会失去抵抗化疗引起的氧化应激的能力，从而更容易出现铁死亡。在这项研究中，我们研究了五蒽酮 A (PXA) 的潜力，它是一种源自红树植物 Acanthus ilicifolius 的内生真菌 Diaporthe goulteri 的呫吨酮二聚体成分，可增强顺铂 (CDDP) 对结直肠癌 (CRC) 的治疗效果通过抑制 Nrf2。本研究报道，PXA 显着提高了 CDDP 抑制 CRC 细胞活性并诱导其凋亡的能力。此外，PXA 被发现会增加 CDDP 引起的氧化应激和 DNA 损伤的水平。此外，Nrf2的过表达逆转了PXA和CDDP联合诱导的DNA损伤和铁死亡。使用斑马鱼异种移植模型的体内实验表明，PXA 增强了 CDDP 对 CRC 的治疗作用。这些研究表明，PXA 增强了 CRC 对 CDDP 的敏感性，并通过抑制 Nrf2 诱导铁死亡，表明 PXA 可能作为联合化疗中的新型抗癌药物。

Ferroptosis has emerged as a potential mechanism for enhancing the efficacy of chemotherapy in cancer treatment. By suppressing nuclear factor erythroid 2-related factor 2 (Nrf2), cancer cells may lose their ability to counteract the oxidative stress induced by chemotherapy, thereby becoming more susceptible to ferroptosis. In this study, we investigate the potential of penexanthone A (PXA), a xanthone dimer component derived from the endophytic fungus Diaporthe goulteri, obtained from mangrove plant Acanthus ilicifolius, to enhance the therapeutic effect of cisplatin (CDDP) on colorectal cancer (CRC) by inhibiting Nrf2. The present study reported that PXA significantly improved the ability of CDDP to inhibit the activity of and induce apoptosis in CRC cells. Moreover, PXA was found to increase the level of oxidative stress and DNA damage caused by CDDP. In addition, the overexpression of Nrf2 reversed the DNA damage and ferroptosis induced by the combination of PXA and CDDP. In vivo experiments using zebrafish xenograft models demonstrated that PXA enhanced the therapeutic effect of CDDP on CRC. These studies suggest that PXA enhanced the sensitivity of CRC to CDDP and induce ferroptosis by targeting Nrf2 inhibition, indicating that PXA might serve as a novel anticancer drug in combination chemotherapy.