Inhibition of NF-kappa B, a Key Inflammatory Protein, Reduced Radiation Toxicity in Zebrafish
Directly inhibiting the activity of a key
protein mediator of inflammation reduced radiation toxicity in zebrafish
embryos, and may ultimately be of help to patients receiving radiation therapy,
according to researchers from the Kimmel Cancer Center at Jefferson.
Reporting in Molecular Cancer
Therapeutics, the researchers found that inhibitors of NF-kappa B (NF-kB)
not only protected against radiation toxicity when given before exposure to
treatment, but also lessened the radiation toxicity when given one to two hours
post-exposure.
In the study, both NF-kB inhibitors and
proteasome inhibitors were examined for their potential to alleviate the
negative effects of radiation. However, the proteasome inhibitors tested, which
included the FDA-approved bortezomib (Velcade), did not show the same effect. In
fact, they actually exacerbated the harmful radiation effects.
“Although proteasome inhibitors
demonstrate activity against NF-kB, they also target many other pathways,” said
Ulrich Rodeck, M.D., Ph.D., professor of Dermatology and Cutaneous Biology at
Jefferson Medical College of Thomas Jefferson University. “We suspect that these
agents may radiosensitize due to inhibition of these other targets.”
This study was led by Dr. Rodeck and Adam
Dicker, M.D., Ph.D., professor and interim chairman of the department Radiation
Oncology at Jefferson.
“We started with the premise that NF-kB
activity might be helpful in protecting cells against the harmful effects of
radiation,” Dr. Rodeck said. “We actually found quite the opposite - inhibiting
the activity is an advantage that increased the survival in zebrafish and
protected the individual organs from harmful effects of radiation.”
According to Dr. Rodeck, the key is to
downmodulate the NF-kB activity, rather than ablating it completely, as
excessive NF-kB activation is potentially detrimental even in the absence of
radiation therapy.
Drs. Rodeck and Dicker will be moving
this research forward so that it may ultimately help individuals exposed to
“dirty bombs,” or cancer patients receiving radiation therapy. Their research
team pioneered using zebrafish embryos as a vertebrate model system to
investigate the effects of radiation therapy.
Media Only Contact:
Emily Shafer
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 9/2/2009