title: Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan. kireihsiao@pie.com.tw.
authors.forename: Kuan Yin
authors.initials: KY
authors.lastname: Hsiao
authors.affiliation: Department of Biomedical Engineering, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan. purple19900104@yahoo.com.tw.
authors.forename: Yi-Jhen
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan. jeff821231@gmail.com.
authors.forename: Zi Nong
authors.initials: ZN
authors.lastname: Liu
authors.affiliation: Department of Electric Engineering, College of Electrical and Information Engineering, I-Shou University, Kaohsiung City 84001, Taiwan. cwchang@isu.edu.tw.
authors.forename: Chin Wen
authors.initials: CW
authors.lastname: Chuang
authors.affiliation: Department of Veterinary Medicine, College of Agriculture, National Chiayi University, Chiayi City 60054, Taiwan. hhuang@mail.ncyu.edu.tw.
authors.forename: Han Hsiang
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan. smkuo@isu.edu.tw.
authors.forename: Shyh Ming
authors.initials: SM
authors.lastname: Kuo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C050253:sinulariolide; D006820:Hyaluronic Acid
keywords: aggregate; hyaluronan; lung adenocarcinoma cells; nanoparticle; sinulariolide