Unveiling the Double-Edged Sword: Polyamines and Their Role in Cancer and Aging

New research has investigated how a family of chemicals called polyamines, known for their anti-aging potential, may also accelerate the growth of cancer cells. The study, conducted by a team from the Tokyo University of Science in Japan, offers insights for both cancer treatment and anti-aging therapies.

The Dual Nature of Polyamines

Polyamines, which include compounds like spermidine and putrescine, are essential molecules in all living cells, regulating cell growth and protein synthesis. Past animal studies have linked spermidine to improved lifespans and health, and it is present in health supplements. However, polyamines have also been associated with cancer spread.

Unraveling Cancer's Exploitation

This study aimed to understand the biological changes involved, particularly how cancer cells utilize sugar without oxygen, even when oxygen is available. This process is known as aerobic glycolysis. The researchers noted that while polyamine metabolism changes correlate with cancer and age-related conditions, the direct modulation of genes affecting cancer progression, specifically aerobic glycolysis-dependent cell growth, remained unclear.

Investigating Key Players: eIF5A Proteins

The study used lab cultures of cervical and breast cancer cells to examine responses to modifications and their effects on proteins eIF5A1 and eIF5A2. While eIF5A1 is crucial for healthy cells, eIF5A2 is associated with cancer growth. Researchers suspected these proteins might explain spermidine's dual role.

The Mechanism Unveiled

By altering polyamine and protein levels in cancer cells using drugs and genetic editing, the study observed that polyamines promote cancer cells towards aerobic glycolysis and increase eIF5A2 levels. This increase occurs by suppressing an RNA molecule, miR-6514-5p, which typically acts as a 'brake' on eIF5A2 production.

Removing polyamines or eIF5A2 from the cells significantly reduced cancer cell growth, while reintroducing spermidine restored the cancer's expansion, indicating a critical role for spermidine in tumor proliferation.

Distinguishing Roles in Health and Disease

Biochemist Kyohei Higashi of Tokyo University of Science elaborated on the differing activities of these proteins:

"In normal tissues, polyamine-activated eIF5A1 activates mitochondria via autophagy. In contrast, in cancer tissues, polyamine-promoted eIF5A2 synthesis controls gene expression at the translational level, facilitating cancer cell proliferation."

Implications for Treatment and Further Research

The research does not suggest polyamines cause cancer but indicates that cancer cells can exploit polyamines for survival and spread once cancer has initiated. The identified roles of eIF5A2 and miR-6514-5p present potential targets for new cancer treatments.

This research, currently limited to cell cultures, requires further investigation to ensure healthy cells are not adversely affected. The findings were published in the Journal of Biological Chemistry.