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Autophagy potential of polyphenols in breast carcinoma: A systematic review
Asal Golchin1, Shirin Teymori Nobari2, Masomeh Maleki3
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
Insights
Polyphenols show promise in inducing autophagy for breast cancer treatment in lab studies. However, translating these findings to effective clinical outcomes remains a significant challenge.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer remains a leading cause of mortality worldwide.
- Autophagy, a cellular degradation process, plays a complex role in cancer progression.
- Polyphenols are natural compounds with potential anti-cancer properties.
Purpose of the Study:
- To systematically review the existing literature on the role of polyphenols in modulating autophagy in breast cancer.
- To identify specific polyphenols and their mechanisms of action in breast cancer cells.
- To assess the translational potential of polyphenol-induced autophagy for breast cancer therapy.
Main Methods:
- A comprehensive systematic search of multiple electronic databases (PubMed, Web of Science, Scopus, EMBASE, Google Scholar) was conducted up to January 1, 2025.
- Keywords included "Breast Cancer," "polyphenols," and "Autophagy," utilizing Medical Subject Headings (MeSH).
- The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Main Results:
- Curcumin modulated the PI3K/AKT/mTOR pathway, enhancing autophagic flux and reducing breast cancer cell viability in vitro.
- Resveratrol targeted the AMPK/mTOR signaling axis, suppressing cancer stem-like cells and inhibiting tumor growth in vivo.
- Carnosol induced autophagy, inhibited metastasis, and reduced tumor growth by degrading STAT3 and downregulating p62.
Conclusions:
- Polyphenols demonstrate significant potential in inducing autophagy within controlled in vitro breast cancer models.
- Translating these in vitro findings to in vivo efficacy and subsequent clinical benefits presents considerable challenges.
- Further research is needed to bridge the gap between laboratory observations and clinical applications of polyphenol-based autophagy modulation in breast cancer.
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