Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells.
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.
['Hsiao|Kuan Yin|KY|', 'Wu|Yi-Jhen|YJ|', 'Liu|Zi Nong|ZN|', 'Chuang|Chin Wen|CW|', 'Huang|Han Hsiang|HH|', 'Kuo|Shyh Ming|SM|']
D000230:Adenocarcinoma D000077192:Adenocarcinoma of Lung D000818:Animals D037421:Anthozoa D000970:Antineoplastic Agents D017209:Apoptosis D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D004224:Diterpenes D004354:Drug Screening Assays, Antitumor D015972:Gene Expression Regulation, Neoplastic D006801:Humans D006820:Hyaluronic Acid D008175:Lung Neoplasms D053758:Nanoparticles
hyaluronan nanoparticle lung adenocarcinoma cells sinulariolide aggregate