Autophagy potential of polyphenols in breast carcinoma: A systematic review.

PURPOSE: This systematic review presents data on the role of polyphenols in autophagy in breast cancer.

METHODS

All research on polyphenol-induced autophagy in breast carcinoma was comprehensively searched in the electronic PubMed, Web of Science, Scopus, EMBASE, and Google Scholar databases up to January 1, 2025. The keywords were searched using the controlled vocabulary (Medical Subject Headings [MeSH]) with the terms Breast Cancer, polyphenols, and Autophagy. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the systematic review and its findings were reported.

RESULTS

Of 742 related publications, a total of 359 items were omitted due to duplication. 58 studies were then manually screened. Ten studies were removed because of insufficient data (n = 6) or not focused on the topic (n = 4). Among the remaining studies (n = 48), 40 in vitro studies were found on breast cell lines and 8 in-vivo studies. Among the in vitro studies, curcumin demonstrated a strong ability to modulate the PI3K/AKT/mTOR pathway, enhancing autophagic flux and reducing cell viability. Resveratrol targeted the AMPK/mTOR signaling axis, showing consistent suppression of cancer stem-like cells and tumor growth inhibition in xenografted models. Carnosol induced autophagy independently of Beclin-1 by degrading STAT3 and downregulating p62, effectively inhibiting metastasis and tumor growth both in vitro and in vivo.

CONCLUSIONS

Most reviewed studies describe in vitro results where polyphenols successfully induce autophagy under controlled in vitro conditions. However, this process is very tricky to translate into an in vivo setting and finally into clinical outcomes.