Timosaponin A-III Induces ROS-mediated Apoptosis and Triggers Protective Autophagy via the AMPK/mTOR Pathway in...

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• Timosaponin A-III (TAIII), derived from Anemarrhena asphodeloides, shows anti-tumor potential.
• Limited research exists on TAIII's effects and mechanisms in prostate cancer (PCa).

Purpose of the Study:

• To investigate the anti-tumor effects of TAIII on PCa cells.
• To elucidate the underlying mechanisms of TAIII's action in PCa.

Main Methods:

• Cell proliferation assessed via CCK-8, colony formation, and EDU assays.
• Apoptosis and reactive oxygen species (ROS) production measured by flow cytometry.
• Autophagy markers (LC3, P62) and AMPK/mTOR pathway proteins analyzed by western blot and immunofluorescence.
• In vivo efficacy evaluated using a PC3 xenograft nude mouse model, with and without chloroquine (CQ).

Main Results:

• TAIII significantly inhibited PCa cell proliferation and induced ROS-dependent apoptosis.
• TAIII treatment increased autophagosome formation (LC3 puncta) and altered LC3B-II/P62 levels.
• Combination therapy with TAIII and CQ enhanced anti-prostate cancer effects in vitro and in vivo.
• TAIII-induced autophagy activation via AMPK/mTOR was confirmed and modulated by Compound C.

Conclusions:

• TAIII exhibits potent anti-prostate cancer activity by inducing apoptosis and autophagy through the AMPK-mTOR pathway.
• TAIII's mechanism involves ROS generation, apoptosis induction, and autophagy modulation.
• Combination of TAIII with CQ presents a potential therapeutic strategy for PCa.
• Further evaluation of TAIII's pharmacokinetics, bioavailability, and toxicity is necessary for clinical application.