白花丹素因其抗炎和抗微生物特性而被用于传统医学。作为一种萘醌，白花丹素会引发活性氧 (ROS) 的产生。体外癌症研究表明，白花丹素通过 ROS 的产生触发癌细胞凋亡。由于癌症介导的慢性炎症会影响骨密度，因此推测白花丹素可能直接抑制骨吸收破骨细胞的形成。我们之前表明，白花丹素对破骨细胞生成的影响在骨髓源性巨噬细胞和巨噬细胞系 RAW 264.7 之间存在差异。尽管RAW 264.7巨噬细胞能够启动破骨细胞生成所需的基因程序，但只有初级巨噬细胞才能成功分化为破骨细胞。在这里，我们发现 RAW 264.7 细胞对白花丹素诱导的细胞凋亡更敏感。在白花丹素和细胞因子 RANKL 存在的情况下，RAW 264.7 巨噬细胞会产生更多的 ROS 并死亡，而 RANKL 会触发 ROS 产生以驱动破骨细胞生成。添加 ROS 清除剂 N-乙酰半胱氨酸可防止细胞死亡，将分化失败与 ROS 水平升高联系起来。 RAW 264.7 细胞的抗氧化应激基因表达减少，而原代巨噬细胞对 ROS 具有更高的耐受性。我们的数据表明，在研究植物化学物质时，考虑细胞（系）固有特性是必不可少的。© 2023 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。

Plumbagin is used in traditional medicine because of its anti-inflammatory and anti-microbial properties. As a naphthoquinone, plumbagin triggers the production of reactive oxygen species (ROS). In vitro cancer studies showed that plumbagin triggers apoptosis in cancer cells through ROS production. As cancer-mediated chronic inflammation can affect bone density, it was hypothesized that plumbagin might directly inhibit the formation of bone-resorbing osteoclasts. We previously showed that the effect of plumbagin on osteoclastogenesis differed between bone marrow-derived macrophages and the macrophage cell line RAW 264.7. Although RAW 264.7 macrophages are able to initiate the gene program required for osteoclastogenesis, only primary macrophages successfully differentiate into osteoclasts. Here, we show that RAW 264.7 cells are more sensitive toward plumbagin-induced apoptosis. In the presence of plumbagin and the cytokine RANKL, which triggers ROS production to drive osteoclastogenesis, RAW 264.7 macrophages produce increased amounts of ROS and die. Addition of the ROS scavenger N-acetyl cysteine prevented cell death, linking the failure to differentiate to increased ROS levels. RAW 264.7 cells show reduced expression of genes protective against oxidative stress, while primary macrophages have a higher tolerance toward ROS. Our data suggest that it is indispensable to consider cell (line)-intrinsic properties when studying phytochemicals.© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.