Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer...

Area of Science:

• Oncology
• Natural Products Chemistry
• Molecular Biology

Background:

• Late-stage castration-resistant prostate cancer (CRPC) presents a significant unmet clinical need due to limited treatment options.
• Novel therapeutic strategies are urgently required to combat advanced prostate cancer progression.

Purpose of the Study:

• To investigate the anticancer effects of Alternol, a natural compound, on advanced prostate cancer cell lines.
• To elucidate the mechanism of Alternol-induced cell death and its efficacy in preclinical models.

Main Methods:

• Prostate cancer cell lines and nonmalignant cells were treated with Alternol.
• Cell viability was assessed using trypan blue exclusion assay.
• Apoptosis was evaluated by detecting caspase-3 processing and PARP cleavage.
• Reactive oxygen species (ROS) involvement was studied using scavengers.
• In vivo efficacy was tested using xenograft mouse models.

Main Results:

• Alternol induced significant cell death in prostate cancer cell lines, but not in nonmalignant cells.
• Alternol-triggered cell death was apoptotic, dose- and time-dependent, involving caspase-3 and PARP cleavage.
• Alternol-induced apoptosis was dependent on reactive oxygen species (ROS) and Bax protein activation.
• Alternol suppressed tumor growth in PC-3 xenografts but not in Bax-null DU-145 xenografts in vivo.

Conclusions:

• Alternol exhibits potent anticancer activity against advanced prostate cancer cells through apoptosis induction.
• The mechanism involves ROS generation and Bax activation, highlighting its potential therapeutic role.
• Alternol demonstrates efficacy in suppressing tumor growth in vivo, suggesting its promise as a novel agent for CRPC.