Antitumor efficacy of the novel chemotherapeutic agent coramsine is potentiated by cotreatment with CpG-containing oligodeoxynucleotides.
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. rvdmost@cyllene.uwa.edu.au
Robbert G
RG
van der Most
Robyn
R
Himbeck
Simon
S
Aarons
Stephen J
SJ
Carter
Irma
I
Larma
Cleo
C
Robinson
Andrew
A
Currie
Richard A
RA
Lake
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004357:Drug Synergism; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D032322:Solanum
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D028321:Plant Preparations; D012991:Solanaceous Alkaloids; C510365:coramsine