Hsiao Kuan Yin, Wu Yi-Jhen, Liu Zi Nong, Chuang Chin Wen, Huang Han Hsiang, Kuo Shyh Ming
Department of Biomedical Engineering, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan.
Department of Electric Engineering, College of Electrical and Information Engineering, I-Shou University, Kaohsiung City 84001, Taiwan.
Molecules. 2016 Mar 2;21(3):297. doi: 10.3390/molecules21030297.
Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL), extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33-77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.
肺癌是全球临床上最具挑战性的恶性疾病之一。从养殖珊瑚物种柔曲柳珊瑚中提取的柳珊瑚内酯（SNL）已被用于抑制恶性细胞。为了开发抗癌治疗药物，我们旨在以SNL为靶向药物寻找非小细胞肺癌治疗的替代方法。我们通过使用高压静电场系统将SNL与透明质酸纳米颗粒缀合以形成HA/SNL聚集体，研究了SNL对A549肺癌细胞的生物活性。SNL对A549细胞有毒性，IC50为75μg/mL。通过细胞活力测定、凋亡测定、细胞周期分析和蛋白质免疫印迹评估了HA/SNL聚集体的抗癌作用。在聚集大量HA纳米颗粒后，HA/SNL聚集体的直径约为33-77nm，具有薄的连续层。流式细胞术分析表明，在25μg/mL的较低SNL剂量下，HA/SNL聚集体诱导的凋亡比纯SNL更有效。蛋白质免疫印迹表明，半胱天冬酶-3、-8和-9以及Bcl-xL和Bax在凋亡信号转导途径中起关键作用。总之，HA/SNL聚集体通过线粒体相关途径对A549细胞发挥了比纯SNL更强的抗癌作用。
