Let there be dark to see nature's cancer drugs
scour nature for its next anticancer drug 'gift'.
A team at the US National Cancer Institute's Center for Cancer Research (CCR), have developed a way of screening hundreds of thousands of biodiverse samples to find a particular diamond in the rough - a naturally occurring anticancer drug. The idea isn't as far-fetched as it might sound, especially when you consider that two widely used anticancer drugs originally came from tree bark and soil bacteria (paclitaxel and rapamycin respectively). In fact, scientists often turn to natural sources to develop new drugs, and the 220,000 samples collected in the NCI's Natural Product Repository are derived from marine organisms, microbes, and plant life gathered from locations across the globe. "The samples in the Repository exist as extracts from specimens that have been collected in the oceans and forests of the world and shipped here - each containing thousands of compounds," said Dr Barry O'Keefe, an NCI researcher. "Somewhere among these samples are natural molecules that have been honed by nature that could have great therapeutic value, but finding them amid the clutter of other natural compounds is difficult." Their latest natural products screen uses an electrochemiluminescent assay, developed by CCR researcher Dr Allan Weissman, which tags the target proteins and causes them to light up when an electrical current is passed through them. If a molecule inhibits the target, then its activity is blocked and the reaction goes dark. To verify that the electrochemiluminescent assay worked properly, the Repository team searched for a molecule that inhibits the known ability of MDM2 to signal for the destruction of the tumour suppressor protein p53. In normal cells, MDM2 and p53 exist in a state of benign equilibrium - balanced to assure that cell suicide does not occur. The researchers screened over 144,000 samples and uncovered almost 2,000 potential hits against MDM2. These were further refined, yielding 372 extracts from which chemists are now isolating active compounds. Among the active compounds recovered, one plant chemical, called sempervirine, was found to induce cell death or apoptosis in cancer cell lines. "Searching through the literature we discovered that sempervirine had been previously considered by French cancer researchers in the 1980s, but since the roles of p53 and MDM2 were poorly understood at the time, sempervirine research took a different direction," O'Keefe said. "Now we will take another look at this compound while we continue to analyze the other extracts." The results were presented at the AACR-NCI-EORTC cancer conference, which finishes today in San Francisco, California.
