Prostate cancer is the most common
cancer in men and the second most common cause of
cancer-related deaths in men. Although, various drugs targeting the
androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and
metastasis of various
cancer cells. In the present study, we investigated effects of
naringenin, a natural
anti-oxidant flavonoid derived from citrus, on
prostate cancer cells (PC3 and LNCaP). Results of present study with PC3 and LNCaP cells revealed that
naringenin inhibited proliferation and migration, while inducing apoptosis and ROS production by those cells. In addition,
naringenin-induced loss of mitochondrial membrane potential and increased Bax and decreased Bcl-2
proteins in PC3 cells, but not LNCaP cells. In a dose-dependent manner,
naringenin decreased phosphorylation of ERK1/2,
P70S6K, S6, and P38 in PC3 cells, and reduced phosphorylation of ERK1/2, P53, P38, and JNK
proteins in LNCaP cells. However,
naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells. Then, targeted signaling
proteins associated with viability of PC3 and LNCaP cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell signaling pathways. Moreover, we compared the apoptotic effects of
naringenin and
paclitaxel alone and in combination to find that
naringenin enhanced the efficiency of
paclitaxel to suppress progression of
prostate cancer cell lines. Collectively, these results indicate that
naringenin is a potential chemotherapeutic agent for treatment of
prostate cancer. J. Cell. Biochem. 118: 1118-1131, 2017. © 2016 Wiley Periodicals, Inc.