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Synergistic Effect Between Curcumin (diferuloylmethane) and Radiation on Clonogenic Cell Death Independent of p53 in Prostate Cancer Cells

Abstract

Bijaya K. Nayak, Naveen K. Krishnegowda, Cynthia A. Galindo, Martin L. Meltz and Gregory P. Swanson

Radiotherapy is a common treatment for prostate cancer, but failure is observed 30 to 40% of the time. It is more common in patients with abnormal p53. The phytochemical diferuloylmethane (curcumin) a naturally occurring fl avinoid derived from the rhizome of Curcuma longa, shows potential radiosensitizing effects. In the present study, the effect of curcumin and radiation on cell viability, apoptosis and clonogenic cell death was examined in LNCaP (wild type p53) and PC3 (mutant p53) prostate cancer cells.

The expression of p53 and p53 target genes was examined using RNase protection assay and Western blot analysis. Cell cycle and apoptosis was evaluated by fl ow cytometry. Cell viability and colony formation was examined using MTT assay and clonogenic assay respectively.

The expression of p53, p21 and gadd45 increased in LNCaP cells after radiation exposure. In PC3 cells, there was no change in expression in mutant p53 after radiation or curcumin treatment. However, the expression of p21 and gadd45 increased after curcumin treatment in PC3 cells independent of p53. Curcumin induced cell growth arrest and apoptosis in both the cell lines. The cell viability and cell proliferation decreased in presence of both curcumin and radiation as compared to curcumin or radiation alone in both the cell lines. Regardless of p53 status, combination treatment with curcumin (2.5 to 10 μM) and radiation (2 Gy) had a synergistic effect on clonogenic cell death in both LNCaP and PC3 cells.

Conclusion: Curcumin appears to radiosensitize prostate cancer cells and may be a possible adjuvant to radiotherapy in the treatment of prostate cancers.