3´-Hydroxypterostilbene suppresses prostate cancer via apoptosis and autophagy in vitro and potent tumor growth inhibition in vivo

Abstract

3´-Hydroxypterostilbene (OHPt), a hydroxylated derivative of pterostilbene (Pt) naturally occurring in dietary plant sources, was evaluated for its anti-prostate cancer potential. In PC-3 cells, OHPt markedly reduced viability in a dose- and time-dependent manner, exhibiting stronger growth inhibition than Pt, implying that hydroxyl substitution at the 3´ position enhances anti-proliferative activity. Mechanistic studies revealed that OHPt triggered both intrinsic and extrinsic apoptosis, evidenced by mitochondrial membrane depolarization, activation of caspase-8, -9, and -3, and an increased Bax/Bcl-xL ratio. Additionally, OHPt promoted autophagic cell death, upregulating Beclin-1, LC3-II expression, and autophagosome formation. In a PC-3 xenograft nude mouse model, OHPt administration significantly suppressed tumor growth without apparent toxicity, accompanied by reduced COX-2 and MMP-9 protein levels and increased LC3-II expression. These findings suggest that OHPt displays strong anti-tumor activity in vitro and in vivo, achieved via coordinated activation of apoptotic and autophagic mechanisms, thereby supporting its potential as a therapeutic candidate for prostate cancer.