Abstract
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.
Highlights
Marine sponges have served as one of the most productive sources of anticancer substances in marine environment[10]
After treatment by stellettin B (Stel B) for 48 h, proliferation of A549 cells was inhibited in a dose-dependent manner (Fig. 1), with the IC50 value as 0.022 μM, suggesting the high inhibitory potency of Stel B
We preliminarily investigated whether A549 cells can develop resistance to Stel B
Summary
Marine sponges have served as one of the most productive sources of anticancer substances in marine environment[10]. As a part of our discovery of new anticancer agents from natural resources, we have been trying to search molecular-targeted antitumor lead compounds from marine sponges[11,12,13,14]. We isolated smenospongine from marine sponge Dactylospongia elegans, and reported the antiproliferative activities on leukemia cells and www.nature.com/scientificreports/. A benzonaphthyridine alkaloid extracted from marine sponge Aaptos suberitoids by us, induced G2/M arrest in chronic myeloid leukemia K562 cells and activated p21 promoter in human osteosarcoma MG63 cells[12,14]. In this paper we report the antitumor effects of Stel B on human NSCLC A549 cells, including the cell cycle G1 arrest, apoptosis and autophagy induction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
