AUTHOR=Choudhuri Rajani , DeGraff William , Gamson Janet , Mitchell James B., Cook John A. TITLE=Guggulsterone-Mediated Enhancement of Radiosensitivity in Human Tumor Cell Lines JOURNAL=Frontiers in Oncology VOLUME=1 YEAR=2011 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2011.00019 DOI=10.3389/fonc.2011.00019 ISSN=2234-943X ABSTRACT=

Purpose: To observe the effect of guggulsterone (GS) on the radiation response in human cancer cell lines. Materials and 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. Conclusion: 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.