Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism

Area of Science:

• Biochemistry
• Oncology
• Cell Biology

Background:

• Limited treatment options for advanced prostate cancer (PCa) necessitate novel therapeutic strategies.
• Mannose, a glucose isomer, exhibits anticancer properties in various tumors, but its role in PCa is not well-defined.

Purpose of the Study:

• To investigate the anticancer effects of mannose on prostate cancer cells in vitro and in vivo.
• To elucidate the underlying mechanisms of mannose-induced cell death in PCa.
• To explore the clinical significance of mannose metabolism in PCa patients.

Main Methods:

• In vitro studies on PCa cell lines assessing proliferation and apoptosis.
• In vivo studies in mice to evaluate anticancer efficacy and safety.
• Mitochondrial function analysis, including membrane potential, ROS levels, and ATP production.
• Western blot analysis for mitochondrial fission proteins (FIS1) and apoptosis-related factors (Bax, Bak).
• Analysis of mannose phosphate isomerase (MPI) expression in PCa patient data.

Main Results:

• Mannose inhibited PCa cell proliferation and induced apoptosis in vitro.
• Mannose demonstrated an anticancer effect in mice without observable toxicity.
• Intracellular mannose accumulation disrupted mitochondrial function, decreasing membrane potential and ATP production while increasing ROS.
• Mannose treatment altered mitochondrial morphology and dysregulated FIS1 expression.
• Mannose enhanced the expression of proapoptotic proteins Bax and Bak.
• Lower MPI expression correlated with poorer PCa prognosis and potentiated mannose's anticancer effect.

Conclusions:

• Mannose exhibits significant anticancer activity against prostate cancer through mechanisms involving mitochondrial dysfunction and apoptosis induction.
• MPI expression levels may serve as a prognostic biomarker in PCa.
• Mannose represents a potential therapeutic agent for prostate cancer, warranting further clinical investigation.