Even the worst things can be good for you. In the right doses, snake venom might hold promise for treating heart disease, and poison from a tropical frog may help relieve pain. Working in this same vein, researchers across the country are testing compounds that are often poisonous and sometimes deadly in the hope of tweaking them to reveal new anti-cancer agents.
The mushroom, with both edible and poisonous varieties, is a common medicinal source, says Robert Hackman, Ph.D., executive director of the Center for Complementary and Alternative Medicine Research at the University of California, Davis.
|
Hackman and others are studying a component of the shiitake mushroom AHCC (active hexose-containing compound) that has been used in Japan for the past 15 years as a cancer treatment.
"In Japan, it's used in conjunction with other traditional chemotherapy regimens," said Hackman, "and with alternative therapies. We're trying to establish how much of what is claimed testimonially can be tested scientifically."
The group is following 60 men with refractory prostate cancer and elevated prostate specific antigen levels to see how they respond to AHCC. If the results are promising, the group will initiate a placebo-controlled study. They will also soon study the compound's effect on bladder cancer.
"The clinical model suggests that AHCC works on cell regulation, so you could at least envision that it would work on all kinds of cancers," said Hackman. In cell culture, he said, AHCC activates natural killer cells and produces a favorable profile of cytokines. "If the AHCC is beneficial, we see it as a complement to conventional medical therapy," he said.
Jack O'Lantern
Trevor McMorris, Ph.D., has been studying another mushroom, the poisonous jack o'lantern, for years. The mushroom's toxic compounds were originally isolated about 35 years ago by the New York Botanical Garden, which was looking for potential antibiotics. The compounds were submitted to the National Cancer Institute for anti-tumor testing and were active, but were not tumor specific.
|
Work so far has led to hydroxymethylacylfulvene (also known by the more manageable monikers of HMAF or MGI 114), derived from illudin-S, one of the original tested compounds. Though one-tenth as toxic as its parent molecule, HMAF has greater selectivity for tumor cells. MGI Pharma, a Minneapolis-based pharmaceutical company, has acquired the rights to all illudin-S analogs, including HMAF.
Animal studies are promising: HMAF produced tumor regressions in 100% of mice with multidrug-resistant lung cancer xenografts, and completely eliminated tumors in 30%.
NCI is sponsoring seven phase II trials of HMAF in cancers including breast, lung, gastrointestinal, and ovarian. MGI Pharma is also completing trials of the compound in pancreatic, prostate, and ovarian cancers.
The venom of the Israeli scorpion, Leiurus quinquestriatus, may be good for more than just paralyzing cockroaches. A peptide of the poison is being tested for activity against one of the most stubborn and deadly cancers glioma.
"What makes [glioma cells] so devastating is that they do not stay localized; they send single cells out into the healthy brain and they remain quiescent and activate after surgery," said Harald Sontheimer, Ph.D., associate professor of neurobiology at the University of Alabama, Birmingham.
Sontheimer and colleagues have found a unique chloride ion channel in the membranes of glioma cells. They believe this channel is involved in the movement of the cells within the brain tissue.
"We have found this receptor in every single glioma tumor and it's so remarkable, because these tumors are so heterogenous," said Sontheimer. The receptor has not been found in any other cell type.
The venom of the Israeli scorpion contains a peptide that binds to the chloride ion channel, inhibiting it. Sontheimer and colleagues have sequenced the peptide and conjugated it with the toxin saporin.
"We use [the scorpion venom protein] as a Trojan horse," said Sontheimer, "to carry a deadly weapon inside these cells."
The group has also conjugated the peptide with radioactive iodine to produce, in essence, highly targeted radiation therapy. Studies of both compounds in mice produced optimistic results. "The compound homes in on the tumors it's extraordinarily promising," said Sontheimer.
The iodine-peptide conjugate will be in clinical trials within the year. If that goes well, Sontheimer said, trials of the saporin-peptide conjugate will begin.
HIV as a Vector?
Researchers are always looking for a better vector for gene therapy, be it for cancer or other diseases. An unusual candidate is the human immunodeficiency virus. HIV's infectiousness makes it ideal, though potentially dangerous.
Inder Verma, Ph.D., and colleagues at the Salk Institute for Biological Studies, San Diego, have disabled HIV by knocking out two-thirds of its genes. They replace the gene for its protein coat which makes HIV specific to T cells with that from a cattle virus, which seems to be able to infect many types of human cells. Verma noted that other genes could be used to make the virus tissue-specific.
|
Verma's lab has used their HIV vector to incorporate genes into liver, muscle, bone marrow, and brain tissues of rats or mice. The inserted genes function for months.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |