mTOR Targeted Cancer Chemoprevention by Flavonoids

Abstract

: Over the past several decades, plant-derived products (phytochemicals) have been suggested to possess immense therapeutic potential. Among these phytochemicals, different flavonoids have been reported for their potent anticancer activity. To exhibit their anticancer potential, these flavonoids modulate different signaling pathways. Among these pathways, the mammalian target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade has been suggested as a pivotal modulator of cell survival, proliferation, and death/apoptosis. Hence, targeting this cascade could be an ideal strategy to alleviate apoptosis and inhibit proliferation in different forms of cancer. The targeting of PI3K/Akt/mTOR by flavonoids have been well documented in the scientific literature. In the current communication, we have covered the anticancer potential of various flavonoids especially flavones, flavanols, and isoflavones that include apigenin, luteolin, biacalein, tangeretin, epigallocatechin-3-gallate, genistein, and diadzein especially dealing with mTOR targeting.

Targeting PI3K/Akt/mTOR Pathway by Different Flavonoids: A Cancer Chemopreventive Approach

“…Natural compounds obtained from plant sources have recently garnered interest due to their easy availability, non-toxic/low adverse effects, cost-effectiveness, and ability to modulate multiple pathways [8]. Among the natural compounds, flavonoids have gained attention as anticancer agents, and are documented as being effective against various types of cancer [9,10]. Flavonoids are of low-molecular-weight, comprising polyphenolic compounds, classified into six groups-isoflavonoids, flavanones, flavanols, flavonols, flavones, and anthocyanidins [11].…”

Polyphenols as anticancer agents: Toxicological concern to healthy cells

“…Daidzein is a 7-hydroxy-3-(4-hydroxyphenyl) chromen-4-one, ubiquitously found in fruits, nuts, soybeans, and related products (Das et al, 2020;Islam et al, 2020). The daidzein leads to slight augmentation in micronucleus development at 75 μM concentration in V79 cells (Di Virgilio, Iwami, Wätjen, Kahl, & Degen, 2004).…”

“…Epigallocatechin-3-gallate is the core catechin present in green tea (Suhail, Parveen, Husain, & Rehan, 2019;Tabrez et al, 2020). Various studies reported different bio-physiological properties of EGCG ranging from antioxidative (Lambert & Elias, 2010;Nikoo, Regenstein, & Gavlighi, 2018), cytoprotective (Islam et al, 2020;Moravcova, Cervinkova, Kucera, Mezera, & Lotkova, 2014), antiinflammatory (Byun et al, 2014;Tabrez et al, 2013), and anti-fibrotic (Tsai et al, 2019;Yumei, Zhou, Zheng, & Chen, 2006). Kucera et al (2015) reported concentration-dependent toxicity of EGCG from 10 μM, whereas 5 μM concentration was suggested as a safer dose for cultured liver cells.…”

“…They are categorized into flavonoids and non-flavonoids and are abundantly found in dietary and/or medicinal plants. Flavonoids are phenolic compounds (containing aromatic rings with one or more hydroxyl groups), ubiquitously present in plants and associated food items (Islam et al, 2020;Stoclet & Schini-Kerth, 2011). During photosynthesis, approximately 2% of all carbon gets transformed into flavonoids or associated compounds.…”

“…During photosynthesis, approximately 2% of all carbon gets transformed into flavonoids or associated compounds. There are two principal forms of flavonoids: attached with one or more sugar moieties and without sugars (Islam et al, 2020).…”