Antitumor Efficacy of the Novel Chemotherapeutic Agent Coramsine Is Potentiated by Cotreatment With CpG-Containing Oligodeoxynucleotides
Wednesday, March 15th, 2006.
Journal of Immunotherapy. 29(2):134-142, March/April 2006. [Link]
van der Most, Robbert G. *; Himbeck, Robyn *; Aarons, Simon *; Carter, Stephen J. +; Larma, Irma *; Robinson, Cleo *; Currie, Andrew *; Lake, Richard A. *
Abstract
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.
Glossary
- immunotherapy
- (im-mune-no-THER-uh-pee) treatments that promote or support the body's immune system response to a disease such as cancer.
- DNA
- (dee-ok-see-ri-bo-new-CLAY-ic) abbreviation for deoxyribonucleic acid. DNA holds genetic information on cell growth, division, and function.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
- apoptosis
- a type of cell death in which the cell basically commits suicide; scientists believe some types of cancer may originate from an interruption of this programmed cell death, allowing cells to grow out of control.
