Dual Role of Polyphenols in Senescence and Cancer: Implications for Anti-Aging and Anticancer Therapies

A summary, written by researchers from the University of Padova, the University of Molise, Queen’s University Belfast and Harvard T. H. Chan School of Public Health, outlines the complex roles of polyphenols in the processes of cell survival, death, and proliferation, particularly focusing on senescent and cancer cells.

Anticancer and longevity mechanisms of quercetin and fisetin

Anticancer and longevity mechanisms of quercetin and fisetin. AKT, protein kinase B; CAT, catalase; CDK1, cyclin dependent kinase 1; COX-2, cyclooxygenase 2; DDX3X, DEAD-box helicase 3 X-linked; ERK1/2, extracellular signal-regulated kinase 1/2; G3BP1, Ras-GTPase-activating protein (GAP)-binding protein 1; GSH, glutathione; GSK3, glycogen synthase kinase 3; hTERT, human telomerase reverse transcriptase; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MMP7, matrix metalloproteinase 7; mTOR, mechanistic target of rapamycin; NF-κB, nuclear factor kappa B; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; SASP, senescence-associated secretory phenotype; SOD, superoxide dismutase.

Cellular senescence, once deemed a permanent halt in cell division due to stressors, is now recognized for its dual role: as a defense mechanism and as a contributor to chronic inflammation and cancer risk through the senescence-associated secretory phenotype (SASP). Senescent cells, which accumulate with age, are characterized by shortened telomeres — a hallmark of aging that, when maintained by telomerase in cancer cells, supports tumorigenesis.

Polyphenols' Impact on Cellular Processes

The review highlights the paradoxical effects of polyphenols, natural compounds with potent bioactive properties, on these cellular processes. While polyphenols generally support telomere maintenance and telomerase activity, contributing to cell survival and longevity, they can also inhibit these processes in cancer cells, promoting cell death. This dual functionality suggests their potential as both anti-aging agents, through direct elimination of senescent cells, and as anticancer agents, by inhibiting SASP and thus indirectly combating cancer.

Bridging Roles and Necessity for Further Research

The significance of this review lies in its comprehensive examination of polyphenols' effects on senescence and cancer, bridging the gap between their anti-proliferative and pro-survival roles. It underscores the necessity for further clinical research into polyphenols, particularly focusing on bioavailability, the influence of gut microbiota on their efficacy, and the establishment of dose-response relationships for therapeutic use.

Promising Applications in Preventive Medicine: Personalized Approach and Potential Conditions

The review also points to the promising applications of polyphenols in preventive medicine, suggesting a personalized approach to dietary integration for the prevention of cancer, aging, and chronic inflammatory conditions, while calling for more research into their pharmacokinetics and long-term usability in preventive strategies.

Read the full paper.

Polyphenols Applications 2024 will highlight the role of polyphenols in health and diseases - with a focus on cancer and aging. Don't miss the chance to join the 16th World Congress on September 19-20, 2024 at the University of Milan, Italy!

Picture credits: Vincenzo Sorrenti et al., 2023.

Copyrights: Polyphenols Applications 2024.

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