Triapine shows promise in treating breast cancer
Published on October 29, 2012

Students at Tennessee Tech University are developing and testing a
series of chemical compounds that show promise of stopping cancer in
its tracks.

A research team comprised mainly of undergraduate TTU students is
producing and analyzing several series of new potent anti-cancer
agents based on an existing anti-cancer drug, Triapine, which is
undergoing clinical trials around the world. Triapine is a chemical
a class of compounds called thiosemicarbazones, which stop tumor cell
growth by blocking enzymes needed for cell replication.

The TTU students are working with chemistry professor Edward Lisic to
determine the minimum dosage needed to be effective.

"Most cancer treatments have unpleasant side effects because the
kill good enzymes too," Lisic said. "The student researchers are
finding that minor modifications to the chemical compounds can change
the efficacy. These new thiosemicarbazone agents may find use in
cancer treatment as stand-alone drugs, or in a cocktail of other
chemotherapy drugs that work together to inhibit or kill cancer cells
and tumors."

The goal is to produce a compound that attacks over-expressed
cancerous enzymes and stops progression of the cancer, without
the good enzymes.

The TTU students are on the front line of drug development in the
at TTU, synthesizing series of new compounds and characterizing them
using state-of-the-art equipment such as nuclear magnetic resonance
spectroscopy and mass spectrometry. The students go to the biology
labs, too, and pipe the compounds into cell cultures to screen how
effectively the compound is stopping cell growth.

At this point in the research, several potent thiosemicarbazone
compounds and their transition metal coordination compounds have been
found to have high activity against enzymes that are required for
replication. TTU is collaborating with two cancer centers, including
the Memorial Sloan-Kettering Cancer Center in New York, for further
studies and possible testing on patients, especially women with
cancer. Breast cancer cells over-express a certain enzyme called
Topoisomerase II for DNA replication, which is specifically targeted
by these new agents.

"We have the personnel and instruments here at TTU that make it
said Lisic. "It takes everybody working together, and the students
really gravitate to this type of research that affects people's lives
and health."

Chemistry and biology majors work side by side in the labs, mentored
by TTU graduate students and doctoral candidates who have been
with Lisic for a while. Lisic started focusing on the anti-cancer
elements of thiosemicarbazone compounds about five years ago.

"Students are excited to be involved in meaningful research that
the promise of positively affecting people's lives, and contributing
to the overall body of scientific and medical knowledge," Lisic said.
"I have also seen that the involvement of students in research
their outlook on life, and helps them focus on their career choices.
They become dedicated to their work and to helping others."

Source: Tennessee Tech University


DNA synthesis disruption is due in part to the effective ability of
Triapine® to chelate iron intracellularly.

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