Please use this identifier to cite or link to this item:
標題: A Soft Coral-Derived Compound, 11-Dehydrosinulariolide, Induces G2/M Cell Cycle Arrest and Apoptosis in Small Cell Lung Cancer
作者: Lin, Yu-Chao
Su, Jui-Hsin
Lin, Shih-Chao
Chang, Chia-Che
Hsia, Te-Chun
Tung, Yu-Tang
Lin, Chi-Chien
關鍵字: 11-dehydrosinulariolide;apoptosis;cell cycle arrest;small cell lung cancer;soft coral;Animals;Anthozoa;Antineoplastic Agents;Apoptosis;Cell Line, Tumor;Cell Proliferation;Disease Progression;Diterpenes;Female;G2 Phase Cell Cycle Checkpoints;Humans;Injections, Intraperitoneal;Lung Neoplasms;Mice;Mice, Inbred BALB C;Mice, Nude;Small Cell Lung Carcinoma;Treatment Outcome;Xenograft Model Antitumor Assays
Project: Marine drugs, Volume 16, Issue 12
11-Dehydrosinulariolide, an active compound that is isolated from the cultured soft coral Sinularia flexibilis, has been suggested to show anti-tumor biological characteristics according to previous studies. However, its potential effect on small cell lung cancer (SCLC) remains unknown. The present study investigates the underlying mechanism for the treatment of SCLC in vitro and in vivo. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was applied to evaluate cell cycle distribution and apoptosis. The expression of proteins related to the cell cycle and apoptosis was analyzed by Western blot analysis. Additionally, an in vivo study was performed to determine the anti-SCLC effect on an H1688 subcutaneous tumor in a BALB/c nude mouse model. 11-Dehydrosinulariolide inhibited cell growth, triggered G2/M arrest and induced H1688 cell apoptosis in a dose- and time-dependent manner. Additionally, 11-dehydrosinulariolide caused the accumulation of p53 and Bax, accompanied by the activation of DNA damage-inducing kinases, including ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2). Moreover, 11-dehydrosinulariolide increased the activity of caspase-3 and -7, suggesting that caspases are involved in 11-dehydrosinulariolide-induced apoptosis. 11-Dehydrosinulariolide also increased the level of tumor suppressor phosphatase and tensin homolog (PTEN) and inhibited the expression of phosphorylated Akt. In the in vivo study, the intraperitoneal injection of 11-dehydrosinulariolide at a dosage of 10 mg/kg significantly inhibited tumor growth compared with the control treatment. Together, the data indicate that 11-dehydrosinulariolide induces G (2)/M cell cycle arrest and apoptosis through various cellular processes, including the upregulation of p53 and Bax, activation of ATM and Chk2, activation of caspase-3 and -7, and accumulation of PTEN, leading to inhibition of the Akt pathway. These findings suggest that 11-dehydrosinulariolide might serve as a promising chemotherapy drug in the treatment of SCLC.
DOI: 10.3390/md16120479
Appears in Collections:生物醫學研究所

Files in This Item:
File Description SizeFormat Existing users please Login
348.pdf7.76 MBAdobe PDFThis file is only available in the university internal network    Request a copy
Show full item record

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.