Results of a small preclinical study conducted at the Karmanos Cancer Center in Detroit indicate that the oral anesthetic dyclonine may enhance the anti-myeloma activity of Velcade.

Dyclonine is the active ingredient in the Sucrets brand of sore throat lozenges, which are sold over-the-counter in drugstores and other retailers in Canada and the United States.  Sucrets lozenges are marketed by Insight Pharmaceuticals.

The Karmanos researchers conducted laboratory tests of dyclonine's activity against the so-called "RPMI8226" line of myeloma cells, which is commonly used in pre-clinical testing of potential myeloma therapies.  The study involved two variants of the RPMI8226 cell line: the standard variant, and a Velcade  ^[1](bortezomib)-resistant variant.

The researchers exposed samples of the RPMI8226 myeloma cells to solutions that had different con­cen­tra­tions of dyclonine alone, Velcade alone, and dyclonine and Velcade combined.

They found that dyclonine alone had limited anti-myeloma activity.  However, when dyclonine was combined with Velcade, the combination was much more effective at killing RPMI8226 myeloma cells than Velcade alone.  The addition of dyclonine, the authors write in their paper, "substantially enhanced the cytotoxic effects of bortezomib [Velcade]."

In addition, the combination of dyclonine and Velcade also was effective at killing many of the Velcade-resistant strain of RPMI8226 myeloma cells.   This occurred, however, only in instances when the con­cen­tra­tion of Velcade in the two-drug combination was considerably higher than was necessary to kill RPMI8226 cells not resistant to Velcade.

Thus, while dyclonine may theoretically make it possible for Velcade to treat myeloma cells that are other­wise resistant to Velcade, the dose of Velcade required to overcome the resistance may be too high to be practical given the side effects patients would likely experience.

The authors of the study decided to investigate the potential anti-myeloma activity of dyclonine combined with Velcade based on the results of an earlier study they had carried out.

In that study, the researchers combined dyclonine with MG132, an experimental breast cancer drug from the same general class of drugs – proteasome inhibitors – that includes Velcade as well as the newer anti-myeloma therapy Kyprolis ^[2] (carfilzomib).  Adding dyclonine to MG132 in the laboratory tests enhanced MG132's effectiveness at killing breast cancer cells.

The results of the previous study, combined with those from the current study, indicate that dyclonine may generally enhance the anti-cancer activity of proteasome inhibitors such as Velcade and Kyprolis.

Although the results of the current study are certainly intriguing, they should be viewed as very preliminary. The study was carried out entirely in the laboratory and entirely in a test tube-like environment.  There was no testing of the dyclonine-Velcade combination against myeloma cells in laboratory animals, let alone in patients with multiple myeloma.

In addition, the study tested the activity of the dyclonine-Velcade combination against just a single myeloma cell line.  Many pre-clinical studies of potential myeloma therapies test the therapies against several mye­lo­ma cell lines, in both test tube environments and in laboratory animals.

It is also the case, unfortunately, that many potential myeloma therapies show early promise in such pre-clinical testing, but then fail to show significant activity when tested in multiple myeloma patients.

Despite these limitations, the Karmanos study raises the interesting possibility that a commonly avail­able over-the-counter drug could enhance the effectiveness of an existing, frequently used myeloma therapy.

For more information, please refer to the study by Ju, D. and Xie, Y., “Dyclonine enhances the cytotoxic effect of proteasome inhibitor bortezomib in multiple myeloma cells,” in Molecular Medicines Report, August, 28, 2014 (online) (abstract ^[3]).