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Tumor Cells Made More Sensitive To Radiation By Blocking A Key Cellular Molecule

Date:
October 25, 2000
Source:
University Of North Carolina School Of Medicine
Summary:
In recent years, cancer researchers have sought ways to make tumors more receptive to treatment. In a series of novel experiments, scientists at the University of North Carolina at Chapel Hill have succeeded in making tumor cells more sensitive to destruction by radiation therapy.
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In recent years, cancer researchers have sought ways to make tumors more receptive to treatment. In a series of novel experiments, scientists at the University of North Carolina at Chapel Hill have succeeded in making tumor cells more sensitive to destruction by radiation therapy.

This was accomplished in colorectal tumor cells by two experimental interventions aimed at blocking activation of a cellular protein, NF-kappaB.

The findings will be detailed in Boston, Wednesday, October 25, at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

Earlier research has shown that activation of the molecule in some tumor types inhibits the cellular self-destruction process called apoptosis. Moreover, ionizing radiation, which is used against malignancies, and some anti-cancer drugs, also may induce NF-kappaB activation.

"This can reduce the cell-killing effects of chemotherapy or radiation," said Joel E. Tepper, MD, head of radiation oncology at UNC-CH School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center. "But it's also known you can inhibit the inhibition of apoptosis. And if you can do that, you may be able to do a more effective job of killing tumor cells with standard anticancer therapies."

The UNC experiments were aimed at determining if the effects of radiation would be enhanced against tumor cells in which NF-kappaB activation was inhibited. Suzanne M. Russo, MD, a former radiation oncology resident at UNC, and now a radiation oncologist at Wake Forest University led the study. Collaborators included Tepper and other Lineberger Center members Albert S. Baldwin, PhD, and James C. Cusack, MD.

The team investigated colorectal tumor cells in lab dishes and in tumors grown on mice. In carefully controlled experiments, they studied two methods of inhibiting NF-kappaB activation. One is the experimental drug PS-341, a proteosome inhibitor chemical that prevents the cell from degrading or breaking down another molecule, IkappaB. This molecule is attached to NF-kappaB and blocks it from activating. Much like a car's brakes, IkappaB stops NF-kappaB from moving into the nucleus, the cell's master control room.

The researchers also studied the effects of infusing tumor cells with a type of IkappaB that is a super-repressor of NF-kappaB. This super-repressor molecule when ferried into tumor cells via an inactivated cold virus creates a very stable attachment to NF-kappaB.

"We were able to determine that NF-kappaB inhibition by either method did in fact produce increased cell killing after radiation," Tepper said. "And we could document both increased cell killing and increased apoptosis."

Moreover, both Tepper and Russo point out that they also documented a decrease in "clonogenic survival." After treatment, tumor cells eventually ceased to divide and died. "This is the most important endpoint," Tepper said.

"We found that treatment with IkappaB super-repressor or PS-341 increased the radiation response," Russo said. "And when we went in vivo to look at mouse models and did the same interventions with tumors we grew on mice, we found the same thing.

"Potentially, agents that modify programmed cell death are exciting in that they may enhance the effects of our current anti-tumor therapies. As demonstrated by this study, radiation may work better in the presence of one of these agents."


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The above story is based on materials provided by University Of North Carolina School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University Of North Carolina School Of Medicine. "Tumor Cells Made More Sensitive To Radiation By Blocking A Key Cellular Molecule." ScienceDaily. ScienceDaily, 25 October 2000. <www.sciencedaily.com/releases/2000/10/001025072224.htm>.
University Of North Carolina School Of Medicine. (2000, October 25). Tumor Cells Made More Sensitive To Radiation By Blocking A Key Cellular Molecule. ScienceDaily. Retrieved May 22, 2015 from www.sciencedaily.com/releases/2000/10/001025072224.htm
University Of North Carolina School Of Medicine. "Tumor Cells Made More Sensitive To Radiation By Blocking A Key Cellular Molecule." ScienceDaily. www.sciencedaily.com/releases/2000/10/001025072224.htm (accessed May 22, 2015).

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