Melatonin effects on ANDROGEN-SENSIVITE and -INSENSITIVE prostate cancer cells under hyperglycemic conditions

Abstract

Experimental diabetes leads to drastic prostatic atrophy and impairment of secretory capacity. This damage is associated with the imbalance in epithelial kinetics, remodeling of the extracellular matrix and morphofunctional changes in prostatic stromal cells. There was also increase incidence of intraepithelial neoplasia (PIN) and incidence of malignancies in the prostate after three months of diabetes. However the association of diabetes and prostate cancer is still controversy. These alterations are related to insulin lack, androgen fall and low intracellular levels of glucose. However, it is important not neglecting the hyperglycemia effects which indirectly culminate in increased oxidative stress. Melatonin (MLT), besides being a potent antioxidant and anti-inflammatory, possesses antiproliferative properties which are well described for prostate cancer cells. However, androgen-dependent prostate cancer cells exhibit different sensitivity to MLT comparing to the androgen-independent. Studies performed by the pHD student demonstrated the in vivo antioxidant role of MLT in the prostate gland of streptozotocin-induced diabetic rats at short- and long-term. This same research showed that prolonged administration of low MLT doses to two-month-diabetic rats led to a decrease in apoptotic rates, increase of cell proliferation, normalization of AR-positive cell frequency and serum testosterone levels. There is a shortage of studies with prostate cancer cells under hyperglycemic conditions. Besides the importance the abroad internship for career development and higher quality of the investigation, it is relevant to analyze the isolated action of MLT in androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cells under hyperglycemic conditions for better understanding of the data we have already obtained in our in vivo studies. This study will analyze if hyperglycemic medium interferes in MLT action on proliferation and apoptotic response of androgen-dependent (LNCaP) and -independent (PC3) prostate cell lines. The application of two different cell lines will clarify if these mechanisms are regulated by androgen signaling under such conditions. (AU)