Views:8 Author:Golden Horizon Biologics Publish Time: 2016-09-13 Origin:Golden Horizon Biologics
More than 20 years ago, a billboard in China piqued the interest of a chemical biologist. It endorsed an extract from the plant known as the ‘thunder god vine’ as an immunosuppressant. A brief review of published research revealed that the extract’s key ingredient-the small molecule triptolide - had been identified 20 years before that billboard ad, and it could stop cells from multiplying.
Now, that chemical biologist and his colleagues at the Johns Hopkins University School of Medicine report that tests of triptolide in human cells and mice are vastly improved by the chemical attachment of glucose to the triptolide molecule. The chemical add-on makes the molecule more soluble and essentially turns it into a ‘cruise missile’ that preferentially seeks out cancer cells, the research says. The change might also decrease side effects in patients and make the drug easier to administer.
A summary of the research is published in the journal Angewandte Chemie and was published online on Aug. 30.
“We have a long way to go before we can test this derivative of triptolide in humans, and we think that additional adjustments could improve it even more,” says Jun O. Liu, Ph.D., professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center, “but it already has the key characteristics we’ve been looking for: It is quite water soluble, and it prefers cancer cells over healthy cells.”
Liu, a native of a small town north of Shanghai in China, explains that the thunder god vine has been used in traditional Chinese medicine for more than 400 years, mostly to calm an overactive immune system, which can cause diseases like rheumatoid arthritis and multiple sclerosis.
His laboratory specializes in figuring out how natural compounds with known healing properties exert their effects on human cells. Five years ago, he and his colleagues discovered that triptolide halts cell growth by interfering with the protein XPB, part of the large protein machine transcription factor IIH, which, in turn, is needed by enzyme complex RNA polymerase II to make mRNA.
Because triptolide halts cell growth, it works well to fight the multiplication of cancer cells, Liu says, both in lab-grown cells and in laboratory animals with cancer. Unfortunately, it - and many of its derivatives - has failed to work well in patients because it doesn’t dissolve well in water or blood, and has too many side effects due to its indiscriminate killing of healthy cells as well as tumor cells.
Liu’s latest research sought to ‘train’ triptolide to target cancer cells by exploiting the knowledge that most cancer cells make extra copies of proteins, called glucose transporters. Those transporters form tunnels through a cell’s membrane to import enough glucose to fuel rapid growth. By attaching glucose to triptolide, the researchers hoped to trick the cancer cells into importing the cell-killing poison, as had been done successfully with other anticancer drugs.