Researchers have discovered why polyamines, compounds promoted for anti-aging benefits, may also promote cancer growth. The study shows that these molecules activate different proteins in healthy versus cancerous cells, leading to contrasting effects. Led by experts at Tokyo University of Science, the findings were published in the Journal of Biological Chemistry.
Polyamines are naturally occurring molecules found in all living cells, essential for functions like cell growth and specialization. In recent years, spermidine—a type of polyamine—has gained attention for its potential to support healthy aging by stimulating autophagy, a process that recycles damaged cellular components. This effect relies on the protein eIF5A1, which enhances mitochondrial activity.
However, elevated polyamine levels are commonly observed in various cancers, where they correlate with rapid tumor progression. Scientists have long puzzled over this duality: how can the same compounds aid longevity while fueling malignancy?
A team led by Associate Professor Kyohei Higashi from the Faculty of Pharmaceutical Sciences at Tokyo University of Science addressed this question through proteomic analysis of human cancer cell lines. They manipulated polyamine levels using drugs and supplementation with spermidine, then examined over 6,700 proteins. The results, published in Volume 301, Issue 8 of the Journal of Biological Chemistry in 2025, indicate that polyamines primarily enhance glycolysis in cancer cells—the fast conversion of glucose to energy—rather than mitochondrial respiration, which is more relevant to aging.
The study highlighted differences between eIF5A1 and its close relative eIF5A2, which shares 84% amino acid sequence similarity. In healthy cells, polyamines activate eIF5A1 to promote autophagy and energy production. In cancer cells, they boost eIF5A2 and ribosomal proteins such as RPS 27A, RPL36AL, and RPL22L1, which support proliferation by regulating gene expression at the translational level.
"The biological activity of polyamines via eIF5A differs between normal and cancer tissues," Dr. Higashi explained. "In normal tissues, eIF5A1, activated by polyamines, activates mitochondria via autophagy, whereas in cancer tissues, eIF5A2, whose synthesis is promoted by polyamines, controls gene expression at the translational level to facilitate the proliferation of cancer cells."
Further, polyamines were found to inhibit miR-6514-5p, a microRNA that normally suppresses eIF5A2 production, allowing higher levels in cancer contexts.
These insights suggest eIF5A2 as a potential therapeutic target. "Our findings reveal an important role for eIF5A2, regulated by polyamines and miR-6514-5p, in cancer cell proliferation, suggesting that the interaction between eIF5A2 and ribosomes, which regulates cancer progression, is a selective target for cancer treatment," Dr. Higashi noted. This approach could curb tumor growth without disrupting polyamines' benefits in healthy aging.
The research was supported by grants from the Japan Society for the Promotion of Science and other foundations.
