A new drug combination developed to kill melanoma cancer cells travels on nanoparticles, which are several hundred times smaller than the width of a hair. The drug, called CelePlum-777, combines a special ratio of the drugs Celecoxib, an anti-inflammatory, and Plumbagin, a toxin.
Exposed to the drug, the melanoma cells have difficulty overcoming the effect of having more than one active ingredient.
Lead author Raghavendra Gowda, assistant professor of pharmacology at Penn State, says:
“Loading multiple drugs into nanoparticles is one innovative approach to deliver multiple cancer drugs to a particular site where they need to act, and have them released at that optimal cancer cell-killing ratio. Another advantage is that by combining the drugs, lower concentrations of each that are more effective and less toxic can be used.”
New Class Of Drugs
[caption id=“attachment_88978” align=“alignright” width=“320”] Plumbago zeylanica, the plant from whose roots Plumbagin is derived. Credit: Forest & Kim Starr. CC BY 3.0[/caption]
Celecoxib and Plumbagin cannot be administered by mouth, because the drugs do not enter the body well this way and cannot be used together in the ratio needed because of toxicity to the patient.
However, CelePlum-777 can be injected intravenously without toxicity. Because of its small size, it also accumulates inside the tumors where it then releases the drugs to kill the cancer cells.
Senior author Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery, says:
“This drug is the first of a new class, loaded with multiple agents to more effectively kill melanoma cells, that has potential to reduce the possibility of resistance development. There is no drug like it in the clinic today and it is likely that the next breakthrough in melanoma treatment will come from a drug like this one.”
The results involve CelePlum-777 killing cancer cells growing in culture dishes and in tumors growing in mice following intravenous injection. The drug prevented tumor development in mice with no detectable side effects and also prevented proteins from enabling uncontrolled cancer cell growth.
The FDA will require more research before CelePlum-777 can be tested in humans through clinical trials.
The research was funded by National Institutes of Health; the Foreman Foundation for Melanoma Research; the Geltrude Foundation for Melanoma Research; the Penn State Melanoma and Skin Cancer Center; the J. Roland Gilbert, Mary R. Gilbert and Elizabeth A. Gilbert Memorial Fund; the James Paul Sutton Medical Research Fund; and the Penn State Chocolate Tour Cancer Research Fund.
Raghavendra Gowda, Gregory Kardos, Arati Sharma, Sanjay Singh and Gavin P. Robertson Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma Mol Cancer Ther March 1 2017 (16) (3) 440-452; DOI: 10.1158/1535-7163.MCT-16-0285
Gowda, Raghavendra et al. Synergistic inhibitory effects of Celecoxib and Plumbagin on melanoma tumor growth Cancer Letters , Volume 385 , 243 - 250
Image: Sandia National Laboratories