Sam W. Lee and Anna Mandinova of Massachusetts General Hospital have accidentally discovered a compound that kills cancer cells by suppressing enzymes that detoxify free radicals.
A cancer cell may seem out of control, growing wildly and breaking all the rules of orderly cell life and death. But amid the seeming chaos there is a balance between a cancer cell's revved-up metabolism and skyrocketing levels of cellular stress. Just as a cancer cell depends on a hyperactive metabolism to fuel its rapid growth, it also depends on anti-oxidative enzymes to quench potentially toxic reactive oxygen species (ROS) generated by such high metabolic demand.
Scientists at the Broad Institute and Massachusetts General Hospital (MGH) have discovered a novel compound that blocks this response to oxidative stress selectively in cancer cells but spares normal cells, with an effectiveness that surpassed a chemotherapy drug currently used to treat breast cancer. Their findings, based on experiments in cell culture and in mice, appear online in Nature on July 13.
The plant-based compound piperlongumine (PL), derived from the fruit of a pepper plant found in southern India and southeast Asia, appears to kill cancer cells by jamming the machinery that dissipates high oxidative stress and the resulting ROS. Normal cells have low levels of ROS, in tune with their more modest metabolism, so they don't need high levels of the anti-oxidant enzymes that PL stymies once they pass a certain threshold.
Cancer cells generate a lot more toxic reactive oxygen species (ROS) because cancer cells grow at a fast rate. Cancer cells have faster rates of metabolism. So a drug that inhibits the cell's defenses against ROS will selectively cause much higher ROS concentration in cancer cells than in normal cells.
Since normal cells do not generate ROS in quantities that are immediately toxic the drug appears to be highly selective for cancer cells.
The scientists tested PL against cancer cells and normal cells engineered to develop cancer. In mice injected with human bladder, breast, lung, or melanoma cancer cells, PL inhibited tumor growth but showed no toxicity in normal mice. In a tougher test of mice that developed breast cancer spontaneously, PL blocked both tumor growth and metastasis. In contrast, the chemotherapy drug paclitaxel (Taxol) was less effective, even at high levels.
"This compound is selectively reducing the enzyme activity involved in oxidative stress balance in cancer cells, so the ROS level can go up above the threshold for cell death," said Lee, a Broad associate member and associate director of CBRC at MGH. "We hope we can use this compound as a starting point for the development of a drug so patients can benefit."
It'll probably be years before this drug (or drugs like it) get tried in humans in clinical trials. But since this compound is found in pepper plants it might be possible to get the compound outside of medical channels of distribution. If I had fatal cancer I would try to get some of it to try.blockquote>
|Share |||Randall Parker, 2011 July 17 11:04 PM Biotech Cancer|