Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway

• Published in: Scientific reports 2016-05, Vol.6 (1), p.27071, Article 27071
• Main Authors: Wang, Ran, Zhang, Qian, Peng, Xin, Zhou, Chang, Zhong, Yuxu, Chen, Xi, Qiu, Yuling, Jin, Meihua, Gong, Min, Kong, Dexin
• Format: Article
• Language: English
• Subjects: 13/31; 14/63; 38/109; 631/154/436; 692/4028/67/1059/153; 82/1; 82/80; A549 Cells; Animals; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Autophagy - drug effects; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Cell Proliferation - drug effects; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - agonists; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; G1 Phase Cell Cycle Checkpoints - drug effects; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; multidisciplinary; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Porifera - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Science; Signal Transduction; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Triterpenes - isolation & purification; Triterpenes - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep27071

Until now, there is not yet antitumor drug with dramatically improved efficacy on non-small cell lung cancer (NSCLC). Marine organisms are rich source of novel compounds with various activities. We isolated stellettin B (Stel B) from marine sponge Jaspis stellifera and demonstrated that it induced G1 arrest, apoptosis and autophagy at low concentrations in human NSCLC A549 cells. G1 arrest by Stel B might be attributed to the reduction of cyclin D1 and enhancement of p27 expression. The apoptosis induction might be related to the cleavage of PARP and increase of ROS generation. Moreover, we demonstrated that Stel B induced autophagy in A549 cells by use of various assays including monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), tandem mRFP-GFP-LC3 fluorescence microscopy and western blot detection of the autophagy markers of LC3B, p62 and Atg5. Meanwhile, Stel B inhibited the expression of PI3K-p110 and the phosphorylation of PDK1, Akt, mTOR, p70S6K as well as GSK-3β, suggesting the correlation of blocking PI3K/Akt/mTOR pathway with the above antitumor activities. Together, our findings indicate the antitumor potential of Stel B for NSCLC by targeting PI3K/Akt/mTOR pathway.