In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol

Robert Michael Hermann^*¹^,5 , Hendrik Andreas Wolff^*¹^,5 , Hubertus Jarry²^,5 , Paul Thelen³^,5 , Carsten Gruendker⁴^,5 , Margret Rave-Fraenk¹^,5 , Heinz Schmidberger⁵ and Hans Christiansen¹^,5

¹Department of Radiotherapy and Radiooncology, University hospital Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany

²Department of Experimental Endocrinology, University hospital Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany

³Department of Urology, University hospital Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany

⁴Department of Gynecology, University hospital Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

⁵Department of Radiotherapy, University of Mainz, Langenbeckstr, 1, 55131, Mainz, Germany

author email corresponding author email* Contributed equally

Radiation Oncology 2008, 3:19doi:10.1186/1748-717X-3-19


Published:	14 July 2008

Abstract

Background

As the majority of prostate cancers (PC) express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein) on the radiosensitivity of PC cells in vitro.

Methods

PC cells LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated. Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 μM and estradiol 10 μM 24 h before irradiation and up to 24 h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed.

Results

LNCaP expressed both ER-α and ER-β, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 μM) stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 μM and estradiol 10 μM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy.

Conclusion

We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-α and ER-β positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-α and ER-β negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular mechanisms, further studies are needed.