Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines.
OBJECTIVE
To observe the effect of guggulsterone (GS) on the radiation response in human cancer cell lines.


METHODS
The radiation response of cancer cells treated with GS was observed by cell survival studies, cell growth assay, NF-κB activity assay, western blotting of some key growth promoting receptors, the DNA repair protein γH2AX, and flow cytometry for DNA analyses.


RESULTS
GS inhibited radiation induced NF-κB activation and enhanced radiosensitivity in the pancreatic cell line, PC-Sw. It reduced both cell cycle movement and cell growth. GS reduced ERα protein in MCF7 cells and IGF1-Rβ protein in colon cancer cells and pancreatic cancer cells and inhibited DNA double strand break (DSB) repair following radiation.


CONCLUSIONS
GS induced radiation sensitization may be due to several different mechanisms including the inhibition of NF-κB activation and reductions in IGF1-Rβ. In addition, GS induced γH2AX formation, primarily in the S-phase, indicates that DNA DSB's in the S-phase may be another reason for GS induced radiosensitivity. ERα down-regulation in response to GS suggests that it can be of potential use in the treatment of estrogen positive tumors that are resistant to tamoxifen.
Radiation Biology Branch, Center for Cancer Research, National Cancer Institute Bethesda, MD, USA.
Rajani
R
Choudhuri
William
W
Degraff
Janet
J
Gamson
James B
JB
Mitchell
John A
JA
Cook