The Emerging Clinical Role of Spermine in Prostate Cancer

Abstract

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management.

Metabolic Phenotyping in Prostate Cancer Using Multi-Omics Approaches

“…Furthermore, the authors observed relevant associations between reduced putrescine levels and upregulation of spermidine synthase (SRM), as well as lower spermine and increased spermidine/spermine N1-acetyltransferase 1 (SAT1) and spermine oxidase (SMOX) expression. In agreement with these results, other authors also reported a reduction in spermine and putrescine levels [34,58,74,75], as well as an overexpression of enzymes involved in the polyamine pathway [83][84][85].…”

The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies

“…Surprisingly, subjects with both radiographic and biochemical recurrence expressed a marginally significant increase of SAT1/2 level in prostate tissue than those without recurrence [34]. Though the change in SAT1/2 levels could compromise different cellular responses, for instance polyamine oxidation [34,35], it served as potential mechanism for the decrease in spermine concentrations in body fluids and tissues, as well as a diagnostic biomarker for prostate cancer [36].…”

Dual Effect of Tryptamine on Prostate Cancer Cell Growth Regulation: A Pilot Study

“…An elevated urine spermidine level was found in PCa compared with noncancerous controls [ 46 ]. Spermine was shown to inhibit the growth of PCa cells with low-metastatic potential but not those with high-metastatic potential, indicating its regulation effects depend on the metastatic state of PCa cells [ 47 ]. The exact link between the spermine concentration and PCa cell proliferation and metastasis needs further investigation.…”