Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism

Abstract

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro , and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.

Mannose metabolism and immune regulation: Insights into its therapeutic potential in immunology-related diseases

“…By contrast, mannose had no significant inhibitory effect or only a weak effect on the growth of tumor cells containing higher PMI levels by interfering with PMI expression via RNA interference, thereby rendering the cells sensitive (Gonzalez et al, 2018). Zhong et al (2022) obtained comparable findings that regarding the role of mannose in advanced prostate cancer (PCa). Mannose inhibits PCa cell proliferation and promotes apoptosis.…”

“…Mannose-treated PCa cells altered mitochondrial morphology and diminished the mitochondrial fission protein FIS1. Furthermore, low expression of PMI-a key enzyme of mannose metabolism-was associated with a poor prognosis in PCa patients, whereas downregulation of PMI expression in PCa cells increased the anticancer effect of mannose (Zhong et al, 2022). Cancer metabolism is temporally and spatially heterogeneous.…”

ACOX2 Serves as a Favorable Indicator Related to Lipid Metabolism and Oxidative Stress for Biochemical Recurrence in Prostate Cancer

“…The protein expression levels of ACOX2 in prostate tissues were examined by IHC, as reported previously 14 . A PCa tissue microarray (TMA; MPR803, Taibsbio, Xi'an, China) was applied in the assay.…”

“…Cell viability was measured using a Cell Counting Kit-8 (CCK-8; CCK8-500T, Meilunbio, Dalian, China) as described previously 14 .…”

“…The colony formation ability of cells was detected through a colony formation assay, as reported previously 14 . Briefly, 1500 PC-3 cells and 3000 22Rv1 cells were seeded in 6-well plates and cultured for 10 days.…”