Although
radiation therapy is commonly used for treatment for many human diseases including
cancer, ionizing radiation produces
reactive oxygen species that can damage both
cancer and healthy cells. Synthetic
triterpenoids, including
CDDO-Me, act as anti-inflammatory and
antioxidant modulators primarily by inducing the
transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if
CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and
breast cancer cell lines. A panel of normal non-cancerous, partially
cancer progressed, and
cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with
CDDO-Me.
CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for
CDDO-Me to exert these radioprotective effects.
CDDO-Me did not protect
cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations.
CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which
CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or
cancer cell lines. This suggests that use of this oral available, non-toxic class of
drug can protect non-cancerous healthy cells during
radiotherapy, resulting in better outcomes and less toxicity for patients.