Abstract: Objective: To investigate the protective effect and underlying mechanism of astaxanthin on oxidative stress induced by hydrogen peroxide in PC-3 cells. Methods: A cellular model of oxidative stress was established by inducing PC-3 cells with H2O2, and pretreatment of PC-3 cells was conducted using astaxanthin at different concentrations. Then, the changes in cell viability, apoptosis, reactive oxygen species (ROS) levels, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 expression and the mitogen-activated protein kinases-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 (MAPK-Nrf2-HO-1) signaling pathway were investigated. Results: Astaxanthin at 20 μmol/L significantly increased cell viability, decreased the accumulation of intracellular ROS, and inhibited the decrease of Bcl-2/Bax ratio and the activation of caspase-3, consequently reducing the apoptosis rate from 51.4% to 14.8%. Our further study showed that astaxanthin could promote the phosphorylation of Nrf2 and the expression of HO-1 in a concentration dependent manner. Pretreatment with extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and Akt inhibitor LY294002 decreased Nrf2 expression by inhibiting ERK and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways, suggesting that the up-regulation of HO-1 expression was mediated by the upstream ERK and PI3K/Akt signaling pathways. Cell viability decreased significantly when the ERK signaling pathway was inhibited, while inhibition of the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways did not affect the protective effect of astaxanthin, which demonstrated that astaxanthin could improve cell viability through the ERK signaling pathway, but not the JNK or p38 MAPK signaling pathway. Conclusion: Astaxanthin can effectively attenuate hydrogen peroxide-induced oxidative stress and maintain the normal physiological activity of PC-3 cells.

Key words: astaxanthin, oxidative stress, PC-3 cell, mitogen-activated protein kinases signaling pathway, nuclear factor erythroid-2-related factor 2, heme oxygenase 1