(NOTE: This story was written in 1996 to report on research that appeared in a journal article at that time. Please understand that while it reports some promising findings, it does not report a cure to cancer. We have not done additional research on this since 1996. Also, please note that we are not interested in purchasing snake venom.)
Writer: Kathleen Davis Phillips, (979) 845-2872, firstname.lastname@example.org
Contact: Dr. Edgar Meyer, (979) 845-1744, email@example.com
COLLEGE STATION — The striking molecular resemblance of enzymes from rattlesnake venom and human cancer cells may help nature bite back at the deadly disease with potent new drugs.
Batimastat, an experimental drug manufactured in Britain, was found to stop the invading cells like “putting a stick in the mouth of an alligator,” according to Dr. Edgar Meyer, a biochemist for the Texas Agricultural Experiment Station. The findings by Meyer’s research team are reported in the April Proceedings of the National Academy of Sciences. The work was a collaboration between Texas A&M; University and Dr. Lance Liotta at the National Cancer Institute’s Pathology Laboratory in Bethesda, Md.
Meyer’s previous observation that the molecular structure of rattlesnake venom enzymes is almost identical to those of human cancer cells has aided research into finding ways to block the spread of cancer by letting the researchers design new inhibitors.
“When venom is injected into a human who is bitten by a snake, the fluid penetrates the surrounding tissue to enter into the blood stream,” Meyer explained. “In the same way, a metastatic tumor cell penetrates surrounding membranes to enter the circulatory system.”
He said the enzymes that make up the venom differ, but the molecules — with some 2,000 atoms — have fundamentally the same structures as a cancer cell. His 3-D models constructed with a special computer program show the structure as a mouth-like opening with an atom of zinc and a molecule of water in the middle. It is that zinc compound in both the cancer cell and snake venom that begins chewing through healthy tissue.
The scientific challenge has been to find a way to block the opening, thus preventing the process from beginning. “If you want to control the degenerative process, you have to go after the zinc,” he said. “It is the mechanism of action.
“It’s like a powerful chain cutter that makes first one snip in a chain-link fence. That weakens the whole fence and the hole can become bigger and bigger until the fence completely breaks down,” Meyer added.
The biochemist noted that cancer as a disease is extremely complex, “but there are steps which define what happens and when. Then you look for inhibitors that are good at stopping that process.”
Understanding this process was possible after Dachuan Zhang, one of Meyer’s graduate students, found a way to grow crystals of the venom enzyme. That gave the team a jigsaw puzzle of atoms that were then pieced together in a 3-D molecular structure on the computer.
Wearing 3-D glasses in Meyer’s lab on the Texas A&M; University campus, the team can visualize “a unique cavity into which the inhibitor has to fit like a ‘lock and key.'”
The research showed that Batimastat binds to the structure deeply in the pocket, thus preventing the venom or tumor cells to begin their destructive work.
Meyer said that though human cancer enzymes are available, the snake venom enzyme was useful in this trial because it is a very stable molecule, readily available and capable of being cloned easily.
A difference with the new experimental drug, he said, is that current methods of chemotherapy “poison” the body, going first for the faster growing cancer cells but causing side effects on the otherwise healthy systems in the body as well. Batimastat is an example of a new generation of drugs developed to go straight to the problem and shut down those harmful enzymes without greatly affecting the others.
In experiments with human, the drug has been injected in solid form which slowly goes into solution (liquifies), he said.
“That’s another challenge (with administering the drug orally). It has to sneak past the digestive and circulatory systems to get to the target,” Meyer added.
He said this new finding is promising, but many questions still are unanswered such as what makes the process of “chomping at healthy cells” begin and, once that process begins, how to make it stop.
The team has a to design such drugs proposal pending with the U.S. National Cancer Institute Cooperative Drug Discovery Group, he said.