Heme-Oxygenase 1: An emerging target in Prostate Cancer.

GUERON G; FERRANDO M; DE LUCA P; DE SIERVI A; VAZQUEZ E

Krakovia, Polonia.

Congreso; Heme Oxygenase International Conference.; 2007

Prostate cancer (PCa), one of the most common cancers in men, is considered a lethal malignancy with increasing incidence worldwide. Although PCa progression is well characterized by the androgen resistant phenotype, little is known about the genetic events of the malignant transformation. Heme Oxygenase 1 (HO-1) could counteract immune-mediated injury either through prevention of oxidative damage or via a local immunomodulatory influence on infiltrating inflammatory cells. Due to the key role that inflammation plays in the development of the tumor and subsequent metastasis, we hypothesize that modulation of HO-1 expression plays a critical role in PCa progression. To better understand the role of HO-1 in PCa, we assessed the expression of this enzyme in PCa cell lines. Western Blot analysis revealed low basal levels in the androgen independent cell line PC3 compared to the androgen sensitive cell line MDA PCa 2b. Treatment of PCa cell cultures with hemin (80 µM, 24h), a potent inducer of HO-1, increased HO-1 protein expression significantly for both cell lines. HO-1 transcriptional induction was also observed for both cell lines under hemin treatment by RT-PCR and qPCR. Moreover, hemin induced HO-1 promoter activity. We further analyzed HO-1 modulation effect on cell proliferation (3H-incorporation), apoptosis (AnnexinV-FITC), and cell cycle regulation. Treatment of PCa cell cultures with hemin had no significant effect on apoptosis but interestingly resulted in a 23% and 45% (p<0.05) reduction in cell proliferation for PC3 and MDA PCa 2b, respectively. Moreover, cell cycle analysis showed a Go/G1 arrest for both cell lines with Hemin (p<0.01). Taken together, these results show HO-1 as a mediator of cell proliferation in prostate cancer and may be implicated in the arrest of these metastatic cell lines, offering a novel therapeutic target for this disease.