Two fluorescent compounds developed by researchers at Vanderbilt University (VU) could help researchers better identify and remove tumor cells well before they become deadly.
According to a study published in Cancer Research, the two molecules selectively bind to and inhibit the activity of an enzyme called cyclooxygenase-2 (cox-2), which is expressed in inflamed tissue and in cancer cells. At the same time, these molecules—called fluorocoxibs—light up the cells making it easier to locate and remove tumors without damaging healthy tissue.
When injected into mice with tumors or inflamed tissue, the glowing fluorocoxibs accumulated in the cancerous or inflamed tissue and could be seen clearly under a microscope. These molecules could help in the removal of tumors before they metastasize and become aggressive cancers.
“Cox-2 is expressed at the earliest stages of pre-malignancy—in pre-malignant lesions, but not in surrounding normal tissue—and as a tumor grows and becomes increasingly malignant, cox-2 levels go up,” said Lawrence Marnett, director of the Vanderbilt Institute of Chemical Biology at VU, in a press release. Marnett led the team that developed the two fluorocoxib molecules.
To create the fluorocoxibs, the researchers developed derivatives of two pain drugs—indomethacin and celecoxib—that bind more selectively to cox-2 than other tested molecules. The team attached several different fluorescent tags to these drug derivatives and created more than 200 potential probes. Each potential probe was tested in inhibition assays containing purified cox-1 and cox-2 enzymes to see which ones would selectively bind to cox-2. Next, the researchers tested the compounds that made the cut in cancer cell cultures. While several compounds inhibited cox-2 in the selection assays, only two were able to do so in cultures.
Although Marnett and his colleagues had previously developed fluorescently tagged cox-2 inhibitors, their earlier attempts could not distinguish between cox-2 and cox-1, a similar enzyme present in most animal cells.
“We’re very excited about these new agents and are moving forward to develop them for human clinical trials,” said Marnett.
As a next step, Marnett’s team is conducting additional toxicological and pharmacological studies to ensure that the molecules can be safely used in cancer patients. They plan to see if these fluorocoxibs could be used to deliver cancer drugs directly to tumors by attaching the drugs to the inhibitors.
The paper “Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents,” was published in the May 1 edition of Cancer Research.