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Natural chromones targeting autophagy signalling pathways as potential anticancer interventions: a systematic review

Shamsudin, Nur Farisya and Mat Nawi, Amira Rusyda and Jantan, Ibrahim and Salim, Emil and Abdullah, Maryam Aisyah and Chia, Suet Lin and Saad, Norazalina and Imran, Syahrul and Leong, Sze-Wei and Nainu, Firzan and Syahputra, Hafid and Syafri, Suryati and Rullah, Kamal (2025) Natural chromones targeting autophagy signalling pathways as potential anticancer interventions: a systematic review. Results in Chemistry, 17 (NA). pp. 1-18. ISSN 2211-7156

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Abstract

Chromones, a class of natural product-based compounds, have garnered considerable interest due to their potential anticancer properties, particularly through the modulation of autophagy. Autophagy is a cellular process involved in both cancer progression and suppression, making it a promising therapeutic target. This systematic review aimed to evaluate the role of chromone-based compounds in regulating autophagy for cancer treatment. A comprehensive search from 2004 to early 2024 yielded 568 records, from which 44 eligible studies were selected based on defined inclusion criteria. These studies collectively investigated 23 distinct phytochemicals, including isoflavones, biflavonoids, prenylated flavones, flavone glycosides, and flavones, providing a robust dataset for evaluating the role of chromones in autophagy modulation. Most compounds activated autophagy, leading to cancer cell death, while a minority triggered autophagic activation with cytoprotective effects. Mechanistically, these compounds primarily inhibited the PI3K/AKT/mTOR pathway, a key regulator of autophagy initiation. This inhibition resulted in increased expression of LC3-II and Beclin-1, which are involved in autophagosome formation, and a decrease in p62 levels, a marker of autophagic degradation. Although the findings demonstrate a strong link between natural chromones and autophagy activation, none of the compounds were found to inhibit autophagy as a means to promote cancer cell death. This strategy, however, has been reported for synthetic derivatives. These results highlight the potential of chromones as anticancer agents and support future research into designing analogues that can selectively activate or inhibit autophagy depending on therapeutic needs.

Item Type: Article (Review)
Uncontrolled Keywords: Chromone-based compounds Anticancer Autophagy PI3K/AKT/mTOR pathway
Subjects: R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy
Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Dr Kamal Rullah
Date Deposited: 19 Dec 2025 09:59
Last Modified: 19 Dec 2025 09:59
Queue Number: 2025-12-Q703
URI: http://irep.iium.edu.my/id/eprint/125482

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