Messenger - Vol. 2, No. 3, Page 13
Summer 1993
On Research
Controlling the body's environmental vigilantes

     Inside the human body, members of one enzyme gang act like
environmental vigilantes, constantly prowling the cell's corridors, always
ready to zap cancer-causing intruders. Dubbed "glutathione S-transferases,"
these vigilante enzymes quickly knock out toxic compounds that invade the
     Unfortunately, in their zeal to get the bad guys, the body's defenders
also knock out cancer-fighting drugs. This is because anti-cancer drugs
must be structurally similar to toxic compounds in order to destroy tumors.
Vigilante enzymes try hard, but they aren't too smart: They can't tell the
difference between dangerous toxic compounds and the drugs sent to kill
     If Roberta F. Colman can prove exactly how glutathione S-transferases
work, the information could lead to new drugs that arrest these enzymes in
cancer patients.
     "Common anti-cancer drugs like Melphalan and Chlorambucil are toxic
compounds that destroy tumors," explains Colman, professor of chemistry and
biochemistry. "However, these drugs are, in turn, decomposed by the
vigilante enzymes, causing them to lose their anti-tumor activity."
     Like all enzymes, glutathione S-transferases act as catalysts,
increasing the rate of chemical reactions within the body.
     Specifically, these vigilante enzymes stimulate a particular region of
the glutathione molecule (found in the liver tissue of mammals) to combine
with various non-soluble foreign substances such as carcinogenic food
preservatives and aflatoxin, which comes from mold. After reacting with
glutathione, these non-soluble, cancer-causing intruders are transformed
into water-soluble substances that can be safely flushed from the body.
     Sadly, the vigilante enzymes also enhance the reaction of glutathione
with drugs used for chemotherapy, rendering them ineffective. To develop
new drugs that temporarily inhibit the enzymes, scientists need a precise
map of the enzymes' "binding pocket."
     So, Colman is tagging portions of vigilante enzymes extracted from rat
livers, to determine how the enzymes' behavior changes when a particular
binding site is blocked. Already, her research has defined several key
regions of activity within the enzymes.
     "A major problem in the treatment of many types of cancer is the fact
that these enzymes cause resistance to chemotherapy drugs," Colman notes.
     "If we could develop inhibitors to specifically target glutathione
S-transferases, these inhibitors could be used to increase the
effectiveness of currently used cancer drugs and so prolong the life of
oncology patients."
                                   -Ginger Pinholster