High density lipoproteins inhibit oxidative stress-induced prostate cancer cell proliferation

Background. Oxidative stress plays a role in the pathogenesis and the progression of prostate cancer (PCa). Reactive oxygen species (ROS) are normally generated within cell metabolism and PCa cells generate a higher amount of ROS proportionally to an aggressive phenotype. High-density lipoprotein (HDL) particles are known to prevent atherosclerosis through different mechanisms, including their antioxidant properties. Aim. To assess in two human PCa cell lines (LNCaP-androgen dependent, and PC3-androgen independent) whether antioxidant properties of HDL were able to reduce oxidative stress and the related cell proliferation. Methods. HDL isolation from plasma of healthy human volunteers, RNA isolation, qPCR, cell proliferation and cell cycle analysis. Results. H2O2 induced oxidative stress in LNCaP (62.6%) and PC3 (27.7%) cells. This effect was counteracted by HDL. A 72-h treatment with 5M H2O2 increased LNCaP (25%) and PC-3 (43%) cell growth. HDL pre-treatment abolished H2O2-driven LNCaP and PC-3 cell proliferation. LNCaP cells seeded at 10% FBS (control) resulted in 82% of cells in G0-G1 phase, 3% in S phase and 15% in G2-M phase. H2O2 incresead G2 phase (25%), whereas concomitant treatment with HDL restored a condition similar to the control. PC-3 cells (control, 5%FBS) showed 64% of cells in G0-G1 phase, 4% in S phase and 32% in G2-M phase. H2O2 treatment increased G2 phase up to 52%, whereas the addition of HDL resulted in cell-cycle phases distribution similar to the control. Conclusions. HDL exert antioxidant activities on androgen-dependent and castration-resistant PCa cell lines, thus limiting cell proliferation induced by ROS.