Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines.

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.

• Authors: Rajani Choudhuri, William Degraff, Janet Gamson, James B Mitchell, John A Cook
• Journal: Frontiers in oncology (Front Oncol) Vol. 1 Pg. 19 ( 2011) ISSN: 2234-943X [Electronic] Switzerland
• PMID: 22649756 (Publication Type: Journal Article)