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

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Radiation Oncology

, 3:19

First Online: 14 July 2008Received: 28 April 2008Accepted: 14 July 2008


BackgroundAs 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.

MethodsPC 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.

ResultsLNCaP 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.

ConclusionWe 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1748-717X-3-19 contains supplementary material, which is available to authorized users.

Robert Michael Hermann, Hendrik Andreas Wolff contributed equally to this work.

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Autor: Robert Michael Hermann - Hendrik Andreas Wolff - Hubertus Jarry - Paul Thelen - Carsten Gruendker - Margret Rave-Fraenk -



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