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Combining
cell replication blocker with common cancer drug kills resistant tumor cells
Combining
cell replication blocker with common cancer drug kills resistant tumor cells
Date:
April 4,
2014
Source:
University of Pittsburgh Schools of
the Health Sciences
Summary:
Researchers have found that an agent that inhibits
mitochondrial division can overcome tumor cell resistance to a commonly used
cancer drug, and that the combination of the two induces rapid and synergistic
cell death. Separately, neither had an effect
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Researchers
from the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC
CancerCenter, have found that an agent that inhibits mitochondrial division can
overcome tumor cell resistance to a commonly used cancer drug, and that the
combination of the two induces rapid and synergistic cell death. Separately,
neither had an effect.
These
findings will be presented Monday at the annual meeting of the American
Association for Cancer Research Annual Meeting 2014.
"In our
earlier work, we found that blocking production of a protein called Drp1
stopped mitochondria, known as the powerhouses of the cell, from undergoing
fission, which is necessary for the cellular division process called
mitosis," said Bennett Van Houten, Ph.D., the Richard M. Cyert Professor
of Molecular Oncology, Pitt School of Medicine, and leader of UPCI's Molecular
and Cell Biology Program. "The loss of this critical mitochondrial protein
caused the cells to arrest in mitosis and to develop chromosomal errors, and
eventually led the tumor cell into the cell death pathway known as apoptosis."
The
researchers blocked Drp1 in breast cancer cell lines with an agent called
mitochondrial division inhibitor-1 (mdivi-1) and found that when mdivi-1 and
the cancer drug cisplatin were given together, they caused DNA damage, DNA
replication stress, and greater than expected apoptosis rates. The synergistic
drug combination acted through two independent biochemical pathways that caused
the mitochondrial membrane to swell, increasing its permeability and allowing
the leak of chemical signals that trigger apoptosis.
"Cisplatin
is one of the most widely used cancer drugs today, but some tumors are
inherently resistant to it, and many others become resistant, leading to
treatment failure," Dr. Van Houten said. "In our studies, this
combination overcame cisplatin resistance and caused cancer cell death, which
is very encouraging."
The team is
testing the regimen's effectiveness in a mouse model of ovarian cancer, a
disease that often recurs and no longer responds to cisplatin treatment.
Story
Source:
The above
story is based on materials provided by University of
Pittsburgh Schools of the Health Sciences. Note: Materials may be
edited for content and length.
Cite This
Page:
University of Pittsburgh Schools of
the Health Sciences. "Combining cell replication blocker with common
cancer drug kills resistant tumor cells." ScienceDaily. ScienceDaily, 4
April 2014. <www.sciencedaily.com/releases/2014/04/140404140213.htm>.