Tryptanthrin, an alkaloid applied in traditional Chinese medicine, exhibits a variety of pharmacological activities. This study aimed to investigate the anti‐tumor activity of the tryptanthrin derivative (8‐cyanoindolo[2,1‐b]quinazoline‐6,12‐dione [CIQ]) in breast cancer cells. In both MDA‐MB‐231 and MCF‐7 breast cancer cells, CIQ inhibited cell viability and promoted caspase‐dependent apoptosis. At the concentration‐ and time‐dependent ways, CIQ increased the levels of p‐ERK, p‐JNK, and p‐p38 in breast cancer cells. We found that exposure to the JNK inhibitor or the ERK inhibitor partially reversed CIQ's viability. We also observed that CIQ increased reactive oxygen species (ROS) generation, and upregulated the phosphorylation and expression of H2AX. However, the pretreatment of the antioxidants did not protect the cells against CIQ's effects on cell viability and apoptosis, which suggested that ROS does not play a major role in the mechanism of action of CIQ. In addition, CIQ inhibited the invasion of MDA‐MB‐231 cells and decreased the expression of the prometastatic factors (MMP‐2 and Snail). These findings demonstrated that the possibility of this compound to show promise in playing an important role against breast cancer.

中文翻译：

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通过 ERK/JNK 激活发现色胺酮衍生的吲哚喹唑啉作为抗乳腺癌药物


色胺酮是一种中药生物碱，具有多种药理活性。本研究旨在研究色胺酮衍生物（8-氰基吲哚[2,1-乙]喹唑啉-6,12-二酮[CIQ]）在乳腺癌细胞中。在 MDA-MB-231 和 MCF-7 乳腺癌细胞中，CIQ 抑制细胞活力并促进 caspase 依赖性细胞凋亡。 CIQ 以浓度和时间依赖性方式增加乳腺癌细胞中 p-ERK、p-JNK 和 p-p38 的水平。我们发现接触 JNK 抑制剂或 ERK 抑制剂可部分逆转 CIQ 的生存能力。我们还观察到 CIQ 增加了活性氧 (ROS) 的产生，并上调了 H2AX 的磷酸化和表达。然而，抗氧化剂的预处理并不能保护细胞免受 CIQ 对细胞活力和细胞凋亡的影响，这表明 ROS 在 CIQ 的作用机制中并不起主要作用。此外，CIQ 抑制 MDA-MB-231 细胞的侵袭并降低促转移因子（MMP-2 和 Snail）的表达。这些发现表明，这种化合物有可能在对抗乳腺癌方面发挥重要作用。