GUTK induces apoptosis in reactivating quiescent prostate cancer cells via Aurora A-mediated stabilization of SOD2

Quiescent prostate Cancer (PCa) cells that survive therapy can later reactivate and drive tumor recurrence and metastasis. Here, we identify a strategy to eliminate these cells during their vulnerable reactivation phase. We show that guttiferone K (GUTK), a bioactive compound isolated from Garcinia yunnanensis Hu, selectively eradicates reactivating quiescent PCa cells by inducing mitochondrial Apoptosis through Caspase activation and loss of mitochondrial membrane potential (ΔΨm). Mechanistically, GUTK suppresses Aurora A recovery and stabilizes SOD2 protein, thereby promoting mitochondrial dysfunction and Apoptosis. SOD2 enhances, whereas Aurora A overexpression attenuates, GUTK-induced cell death. In orthotopic and xenograft prostate tumor models, GUTK combined with docetaxel significantly inhibits tumor growth and suppresses post-chemotherapy recurrence without evident toxicity. These findings identify GUTK as a potential therapeutic agent targeting reactivating quiescent PCa cells and highlight the Aurora A-SOD2 axis as a promising pathway for preventing PCa recurrence.