School of Life Sciences, Northwestern Polytechnical University, Xi'an, China; Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an, China.
School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.
Biochim Biophys Acta Mol Basis Dis. 2023 Aug;1869(6):166740. doi: 10.1016/j.bbadis.2023.166740. Epub 2023 May 2.
Phenethyl isothiocyanate (PEITC), a kind of isothiocyanate available in cruciferous vegetables, exhibits inhibitory effects on cancers. PEITC has been extensively recorded for its effect on regulation of redox status in cancer cells. Our previous studies revealed that PEITC induced ROS-dependent cell death in osteosarcoma. Mitochondria are the main sites for ROS generation and play significant role in deciding cell fate. To dissect the mechanism of PEITC's action on osteosarcoma cells, we detected the changes on mitochondrial network, function and metabolism in K7M2 and 143B cells. Here, PEITC induced cytosolic, lipid and mitochondrial ROS production in osteosarcoma cells. It changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass. Meantime, PEITC increased mitochondrial transmembrane potential in short time, decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. PEITC inhibited proliferation potential of osteosarcoma cells with damage on mitochondrial respiratory chain complexes. Further, PEITC-treated osteosarcoma cells experienced a sudden increase in ATP level, and later its content was decreased. Moreover, PEITC downregulated the expressions of mitochondrial respiratory chain complexes including COX IV, UQCR, SDHA and NDUFA9 in 143B cells and COX IV in K7M2 cells. At last, by using ρ cells derived from K7M2 and 143B cells, we found that osteosarcoma cells that depleted mtDNA were less sensitive to PEITC-induced changes on cellular morphology, cytoskeleton filament, mitochondrial transmembrane potential and ROS generation. In conclusion, our study demonstrated that mitochondria may play important role in PEITC-induced oxidative cell death in osteosarcoma cells.
苯乙基异硫氰酸酯（PEITC）是十字花科蔬菜中存在的一种异硫氰酸酯，具有抑制癌症的作用。PEITC 对调节癌细胞氧化还原状态的作用已有广泛记载。我们之前的研究表明，PEITC 诱导骨肉瘤细胞中 ROS 依赖性细胞死亡。线粒体是 ROS 产生的主要场所，在决定细胞命运方面发挥着重要作用。为了剖析 PEITC 对骨肉瘤细胞作用的机制，我们检测了 K7M2 和 143B 细胞中线粒体网络、功能和代谢的变化。在此，PEITC 诱导骨肉瘤细胞产生细胞质、脂质和线粒体 ROS。它改变了线粒体的形态，从长形变为点状网络，并减少了线粒体的数量。同时，PEITC 在短时间内增加了线粒体跨膜电位，随着时间的延长而降低，随后在 K7M2 细胞中崩溃，在 143B 细胞中降低。PEITC 抑制了骨肉瘤细胞的增殖潜力，同时对线粒体呼吸链复合物造成损伤。此外，PEITC 处理的骨肉瘤细胞的 ATP 水平突然升高，随后其含量降低。此外，PEITC 下调了 143B 细胞中线粒体呼吸链复合物包括 COX IV、UQCR、SDHA 和 NDUFA9 以及 K7M2 细胞中的 COX IV 的表达。最后，通过使用 K7M2 和 143B 细胞衍生的 ρ 细胞，我们发现耗竭 mtDNA 的骨肉瘤细胞对 PEITC 诱导的细胞形态、细胞骨架丝、线粒体跨膜电位和 ROS 生成的变化的敏感性降低。总之，我们的研究表明，线粒体在 PEITC 诱导的骨肉瘤细胞氧化细胞死亡中可能发挥重要作用。
