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Mar. Drugs 2014, 12(3), 1377-1389; doi:10.3390/md12031377
Article

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

1,2
Received: 1 November 2013; in revised form: 17 January 2014 / Accepted: 27 February 2014 / Published: 7 March 2014
(This article belongs to the Special Issue Marine Compounds and Cancer)
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Abstract: 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.
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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Hamilton, G. Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines. Mar. Drugs 2014, 12, 1377-1389.

AMA Style

Hamilton G. Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines. Marine Drugs. 2014; 12(3):1377-1389.

Chicago/Turabian Style

Hamilton, Gerhard. 2014. "Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines." Mar. Drugs 12, no. 3: 1377-1389.


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