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Open AccessArticle

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

1
Ludwig Boltzmann Cluster of Translational Oncology, A-1090, Vienna, Austria
2
Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria 
Mar. Drugs 2014, 12(3), 1377-1389; https://doi.org/10.3390/md12031377
Received: 1 November 2013 / Revised: 17 January 2014 / Accepted: 27 February 2014 / Published: 7 March 2014
(This article belongs to the Collection Marine Compounds and Cancer)
Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS. View Full-Text
Keywords: fascaplysin; cyclin-dependent kinase; small cell lung cancer; cytotoxicity; reactive oxygen species; camptothecin; poly(ADP-ribose)-polymerase inhibitor fascaplysin; cyclin-dependent kinase; small cell lung cancer; cytotoxicity; reactive oxygen species; camptothecin; poly(ADP-ribose)-polymerase inhibitor
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Hamilton, G. Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines. Mar. Drugs 2014, 12, 1377-1389.

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