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Pharmaceutics
Volume 18
Issue 1
10.3390/pharmaceutics18010007
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models

by
Alessandro Maugeri
1,
Paola De Cicco
2,
Rebecca Amico
2,
Martina Farina
3,
Michele Navarra
3,* and
Francesca Borrelli
2
1
Department of Veterinary Sciences, University of Messina, I-98168 Messina, Italy
2
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, I-80131 Naples, Italy
3
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, I-98166 Messina, Italy
*
Author to whom correspondence should be addressed.
Pharmaceutics 2026, 18(1), 7; https://doi.org/10.3390/pharmaceutics18010007 (registering DOI)
Submission received: 7 November 2025 / Revised: 5 December 2025 / Accepted: 17 December 2025 / Published: 20 December 2025
(This article belongs to the Special Issue Pharmaceutical Applications and Therapeutic Mechanisms of Substances from Plant Origin)
Versions Notes

Abstract

Background/Objectives: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Evidence suggests that a polyphenol-rich diet may lower the risk of CRC. The aim of this study was to demonstrate the potential antitumor effects of a flavonoid-rich extract of bergamot juice (BJe) in both in vitro and in vivo CRC models, assessing the underlying mechanisms. Methods: CRC cells, among which HCT-116, have been employed to assess the fine mechanism of action of BJe, whereas a mouse model of azoxymethane (AOM)-induced CRC was exploited to appreciate the anti-cancer effects of BJe. Results: BJe inhibited the growth of several CRC cells, especially HCT-116. In this cell line, BJe induced apoptosis and blocked the cell cycle in the G1 phase, as well as modulated the gene expression of apoptosis- and cell cycle-related factors. Moreover, BJe prompted reactive oxygen species production and impaired mitochondrial membrane potential. In the nucleus of these cancerous cells, BJe induced DNA damage as confirmed by the raised levels of 8-oxo-2′-deoxyguanosine and phosphorylation of histone H2A.X. In mice with AOM-induced CRC, BJe was able to lower the number of aberrant crypt foci. Moreover, BJe reduced the percentage of mice bearing both polyps and tumors, as well as their number. Conclusions: Our study supports the role of BJe against CRC, providing knowledge on the underlying mechanism of action.
Keywords: colorectal cancer; nutraceuticals; flavonoids; bergamot; Citrus bergamia; HCT-116; azoxymethane; mice colorectal cancer; nutraceuticals; flavonoids; bergamot; Citrus bergamia; HCT-116; azoxymethane; mice

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MDPI and ACS Style

Maugeri, A.; De Cicco, P.; Amico, R.; Farina, M.; Navarra, M.; Borrelli, F. Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models. Pharmaceutics 2026, 18, 7. https://doi.org/10.3390/pharmaceutics18010007

AMA Style

Maugeri A, De Cicco P, Amico R, Farina M, Navarra M, Borrelli F. Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models. Pharmaceutics. 2026; 18(1):7. https://doi.org/10.3390/pharmaceutics18010007

Chicago/Turabian Style

Maugeri, Alessandro, Paola De Cicco, Rebecca Amico, Martina Farina, Michele Navarra, and Francesca Borrelli. 2026. "Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models" Pharmaceutics 18, no. 1: 7. https://doi.org/10.3390/pharmaceutics18010007

APA Style

Maugeri, A., De Cicco, P., Amico, R., Farina, M., Navarra, M., & Borrelli, F. (2026). Targeting Redox Homeostasis and Cell Survival Signaling with a Flavonoid-Rich Extract of Bergamot Juice in In Vitro and In Vivo Colorectal Cancer Models. Pharmaceutics, 18(1), 7. https://doi.org/10.3390/pharmaceutics18010007

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