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Antitumor Efficacy of the Novel Chemotherapeutic Agent Coramsine Is Potentiated by Cotreatment With CpG-Containing Oligodeoxynucleotides

van der Most, Robbert G.*; Himbeck, Robyn*; Aarons, Simon*; Carter, Stephen J.; Larma, Irma*; Robinson, Cleo*; Currie, Andrew*; Lake, Richard A.*

doi: 10.1097/01.cji.0000187958.38179.a9
Original Studies

Coramsine is a novel chemotherapeutic agent isolated from Solanum linnaeanum (devil's apple). Topical treatment provides clinical benefit for skin tumors. To evaluate the potential broader applicability of the drug, its in vivo anticancer efficacy in a murine model of malignant mesothelioma and its mode of action were investigated. Systemic administration of coramsine slowed tumor growth and prolonged survival time. Importantly, the antitumor efficacy of coramsine was enhanced when treatment was combined with stimulation of innate immunity using unmethylated CpG-containing oligodeoxynucleotides (ODNs). Combination treatment further slowed tumor growth and provided a survival benefit. Coramsine seems to kill tumor cells by direct cell lysis. Using 2 different assays to detect apoptosis (caspase activation and DNA fragmentation), we found no evidence that coramsine induces any form of programmed cell death. The fact that the efficacy of coramsine is potentiated by CpG ODNs suggests that coramsine-induced cell death is an immunologic null event.

*School of Medicine and Pharmacology and Western Australian Institute for Medical Research, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

Solbec Pharmaceuticals, Osborne Park, Western Australia, Australia

Grant support provided by the Biotechnology Innovation Fund (R. Himbeck and S. Aarons), Raine Foundation (A. Currie), Western Australian Institute for Medical Research (R.G. van der Most), and Insurance Commission of Western Australia (R.A. Lake).

Reprints: Robbert van der Most, School of Medicine and Pharmacology, University of Western Australia, Fourth Floor, G Block, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia (e-mail: rvdmost@cyllene.uwa.edu.au)

Received for publication June 3, 2005; accepted August 10, 2005

© 2006 Lippincott Williams & Wilkins, Inc.