Citation: Farhan, M.; Rizvi, A.; Aatif, M.; Ahmad, A. Current Understanding of Flavonoids in Cancer Therapy and Prevention. Metabolites 2023, 13, 481. https:// doi.org/10.3390/metabo13040481 Academic Editor: Marijana Zovko Konˇ ci´ c Received: 14 February 2023 Revised: 21 March 2023 Accepted: 23 March 2023 Published: 27 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). metabolites H OH OH Review Current Understanding of Flavonoids in Cancer Therapy and Prevention Mohd Farhan 1, * , Asim Rizvi 2 , Mohammad Aatif 3 and Aamir Ahmad 4 1 Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al Ahsa 31982, Saudi Arabia 2 Department of Kulliyat, Faculty of Unani Medicine, Aligarh Muslim University, Aligarh 202002, India 3 Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia 4 Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar * Correspondence: mfarhan@kfu.edu.sa Abstract: Cancer is a major cause of death worldwide, with multiple pathophysiological manifes- tations. In particular, genetic abnormalities, inflammation, bad eating habits, radiation exposure, work stress, and toxin consumption have been linked to cancer disease development and progression. Recently, natural bioactive chemicals known as polyphenols found in plants were shown to have an- ticancer capabilities, destroying altered or malignant cells without harming normal cells. Flavonoids have demonstrated antioxidant, antiviral, anticancer, and anti-inflammatory effects. Flavonoid type, bioavailability, and possible method of action determine these biological actions. These low-cost pharmaceutical components have significant biological activities and are beneficial for several chronic disorders, including cancer. Recent research has focused primarily on isolating, synthesizing, and studying the effects of flavonoids on human health. Here we have attempted to summarize our current knowledge of flavonoids, focusing on their mode of action to better understand their effects on cancer. Keywords: flavonoids; polyphenols; anticancer; apoptosis; molecular mechanisms 1. Introduction A number of studies have pointed to the importance of a plant-based diet in ward- ing off conditions that can lead to cancer [1]. Vegetables contain a number of bioactive components, including phenolic compounds, carotenoids, and, most notably, flavonoids, which may contribute to the plant-based diet’s health advantages. The amount of research focused on exploring flavonoids thoroughly has risen significantly in the most recent years as a result of these potential uses. As a class of phenolic chemicals generated by plants, flavonoids are classified as secondary metabolites. They can be found in a wide variety of photosynthetic species and are particularly prevalent in meals and beverages derived from plants, though their precise makeup varies greatly. Two benzene rings (A and B) are joined to the heterocyclic pyranic ring (C) to form the chemical structure’s 15-carbon skeleton [2]. There are many different types of flavonoids, and they may be broken down into several different classes: anthocyanins, flavones, flavonols, chalcones, isoflavones, flavanones, flavanonols, and flavanols [3]. This difference is due to the degree of unsaturation of the flavone ring and the oxidation of the carbonaceous ring (Figure 1), the key skeletons of the flavonoid. It is challenging to establish epidemiologic correlations regarding the impact of flavonoids on human health versus disease due to the difficulty of estimating dietary intake due to the large quantitative and qualitative heterogeneity of flavonoids in a variety of vegetables and fruits. Flavonoids have been a part of the human diet in almost all geo- graphic regions [4–20]. Details of the geographical consumption of flavonoids are beyond the scope of this review. Metabolites 2023, 13, 481. https://doi.org/10.3390/metabo13040481 https://www.mdpi.com/journal/metabolites