Eriodictyol 5-O-methyl ether inhibits prostate cancer progression through targeting STAT3 signaling and inducing apoptosis and paraptosis

Abstract

Prostate cancer ranks as one of the most prevalent cancers among men and is a major cause of cancer-related mortality globally This study aims to elucidate the molecular mechanisms underlying the anti-cancer effects of eriodictyol 5-O-methyl ether (ERIO) on prostate cancer cells, focusing on its impact on STAT3 signaling, apoptosis, and paraptosis. ERIO exhibited significant cytotoxicity against DU145, PC-3, and LNCaP cells. It suppressed constitutive and IL-6-induced STAT3 activation by inhibiting the phosphorylation of JAK1, JAK2, and Src kinases. ERIO upregulated SHP-2 expression, leading to the dephosphorylation of STAT3. ERIO induced apoptosis, evidenced by increased caspase-3 and PARP cleavage, and paraptosis, characterized by increased ROS production, decreased mitochondrial membrane potential, and ER stress. The antioxidant NAC reversed the effects of ERIO, highlighting the importance of oxidative stress in its anti-cancer activity. ERIO effectively inhibited prostate cancer cell growth by targeting STAT3 signaling and inducing both apoptosis and paraptosis. These findings suggest that ERIO has significant therapeutic potential for prostate cancer treatment and warrant further investigation in in vivo and clinical studies.