Department of Biotechnology, Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Department of Biomedical Sciences, Catholic Kwandong University, Gangneung, Republic of Korea.
J Cell Physiol. 2019 Jun;234(6):9504-9514. doi: 10.1002/jcp.27638. Epub 2018 Oct 26.
Canine osteosarcoma is characterized by aggressiveness, easy metastasis to the lungs, and high mortality after standard therapy. Luteolin is a flavonoid found in vegetables and fruits and has diverse functions. Elucidation of the biological mechanisms of luteolin on canine osteosarcoma will enhance the efficacy of chemotherapeutic agents in canine tumors. In this study, we examined the effects of luteolin in the canine osteosarcoma cell lines, D17 and DSN. The results of this study show that luteolin inhibited canine osteosarcoma cell proliferation and induced apoptosis by altering cell-cycle proportion, producing reactive oxygen species, increasing the loss of mitochondrial membrane potential, and reducing cytosolic Ca concentration. In addition, luteolin activated ERK1/2 and inactivated phosphoinositide 3-kinase/AKT signaling in canine osteosarcoma cells. Moreover, luteolin showed synergistic effects with cisplatin to reduce cell proliferation. In summary, luteolin induced cell death by initiating mitochondrial dysfunction and regulating intracellular signal transduction in canine osteosarcoma cells.
犬骨肉瘤的特点是侵袭性强，易向肺部转移，标准治疗后死亡率高。木犀草素是一种存在于蔬菜和水果中的类黄酮，具有多种功能。阐明木犀草素对犬骨肉瘤的生物学机制将增强化疗药物在犬肿瘤中的疗效。在这项研究中，我们研究了木犀草素对犬骨肉瘤细胞系 D17 和 DSN 的作用。研究结果表明，木犀草素通过改变细胞周期比例、产生活性氧、增加线粒体膜电位丧失和降低胞质 Ca 浓度来抑制犬骨肉瘤细胞增殖并诱导细胞凋亡。此外，木犀草素激活了犬骨肉瘤细胞中的 ERK1/2 并抑制了磷酸肌醇 3-激酶/AKT 信号通路。此外，木犀草素与顺铂具有协同作用，可降低细胞增殖。总之，木犀草素通过引发线粒体功能障碍和调节犬骨肉瘤细胞内信号转导诱导细胞死亡。
