The challenge in treating cancer has been to selectively target cancer cells without harming normal cells. Researchers have found a new drug that appears to do just that—they have discovered that an herbal drug called BZL101 significantly damages cancer cells while sparing healthy cells, and now they think they know how it works.
BZL 101 is an extract from the Chinese medicinal herb, Scutellaria barbata. (Flower of plant is shown at left.) In a phase 1 trial, the drug showed promise in treating advanced breast cancer, but researchers wanted to find out exactly how the drug kills cancer cells, and why it spares healthy cells. “I think it’s very important to know the mechanism of action, because it’s difficult to give patients drugs when you have no idea how they work,” explains lead author Emma Shtivelman, PhD, Director of Cancer Research at BioNovo, Inc in Emeryville, California. “If you know the mechanisms you can target the drug more precisely and predict potential side effects, which are clear goals of research and development.”
Many cancer therapies that kill cancer cells do so by a process of programmed cell death, called apoptosis. But this didn’t seem to be the case with BZL101, which had the researchers wondering as to the real mechanism.
“The buzzword in cancer research for years was apoptosis—and we saw that BZL101 induces a lot of cell death, but we couldn’t describe it as apoptopic cell death,” says Dr. Shtivelman. In a culture of breast cancer cells, only 10 to 15 percent of the cancer cells were killed by apoptosis. For the remainder, there was obviously a different cause at work.
What the researchers found after treating cancer cell lines with BZL101 was that the drug triggers high levels of reactive oxygen species (ROS)—highly unstable molecules that can damage DNA. “Normal cells are well equipped to cope with highly reactive oxygen species because they’re harmful,” according to Dr. Shtivelman. Tumor cells, though, already have high levels of ROS, and the additional ROS induced by BZL101, “takes them overboard and they die,” she says. Also, because the drug inhibits glycolysis—the method cancer cells use to produce energy—it can force them to deplete their energy stores and essentially starve to death, Dr. Shtivelman and her colleagues reported in Cancer Biology & Therapy.
Because it spares healthy cells, BZL101 appears to be very safe overall. The only side effects noted so far have been mild, including constipation, nausea, and diarrhea.
The next phase of the research, which will look at the drug’s effectiveness, is slated to be completed in September 2009. If the results are favorable, the researchers will move on to phase 3 trials with larger groups of patients.
The study authors believe BZL offers great promise over many current cancer therapies because of its low toxicity and limited risk of side effects. “Conventional chemotherapeutic drugs hit all proliferating cells in the body,” says Dr. Shtivelman. “That’s why cancer patients who are on chemotherapy lose their hair, have intestinal problems, and are frequently anemic. If that can be avoided you can increase the dose, if necessary. And with BZL101 that seems to be the case—tumor cells are ready to die when they see the drug and normal cells remain healthy.”
Fong S, Shoemaker M, Cadaoas J, Lo A, Liao W, Tagliaferri M, Cohen I, Shtivelman E. Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells. Cancer Biology & Therapy. 2008;7:7(4).