Title:Hydroxytyrosol Promotes Superoxide Production and Defects in Autophagy Leading to Anti-proliferation and Apoptosis on Human Prostate Cancer Cells
Volume: 13
Issue: 6
Author(s): Cheng Luo, Yan Li, Hui Wang, Yang Cui, Zhihui Feng, Hua Li, Yuan Li, Ying Wang, Karin Wurtz, Peter Weber, Jiangang Long and Jiankang Liu
Affiliation:
Keywords:
Autophagy, hydroxytyrosol, mitochondrial dysfunction, prostate cancer, superoxide.
Abstract: Hydroxytyrosol, an important polyphenolic compound found in olive oil, has shown anti-tumor activity both in
vitro and in vivo. However, effects of hydroxytyrosol on prostate cancer are largely unkown. We found that
hydroxytyrosol preferentially reduces the viability of human prostate cancer cells (PC-3, DU145) compared to an
immortalized non-malignant prostate epithelial cell line (RWPE-1). Exposure of PC-3 cells to 80 µmol/L hydroxytyrosol
resulted in significant increases in both superoxide production and activation of apoptosis. These increases were
accompanied by mitochondrial dysfunction, defects in autophagy, and activation of MAP kinases. Moreover, N-acetylcysteine
(NAC), an efficient reactive oxygen species (ROS) scavenger, was able to reverse the hydroxytyrosol-induced
effects of cell viability loss, defects in autophagy, and activation of apoptosis. This evidence suggests that ROS play a
vital role in the loss of PC-3 cell viability. However, MAPK inhibitors including U0126 (for Erk1/2), SB203580 (for
p38MAPK) and SP600125 (for JNK) did not decrease hydroxytyrosol-induced growth inhibition, suggesting that these
kinases may not be required for the growth inhibitory effect of hydroxytyrosol. Moreover, addition of ROS scavengers
(i.e. NAC, catalase, pyruvate, SOD) in the growth media can prevent hydroxytyrosol induced cell viability loss,
suggesting that extracellular ROS (superoxide and hydrogen peroxide) facilitate the anti-proliferation effect of
hydroxytyrosol in prostate cancer cells. The present work firstly shows that hydroxytyrosol induces apoptotic cell death
and mitochondrial dysfunction by generating superoxide in PC-3 cells. This research presents preliminary evidence on the
in vitro chemopreventive effect of hydroxytyrosol, and will contribute to further investigation of hydroxytyrosol as an
anti-cancer agent.
