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

Abstract

Cancer is, globally, one of the main causes of death. Even though various therapies are available, they are still painful because of their adverse side effects. Available treatments frequently fail due to unpromising responses, resistance to classical anticancer drugs, radiation therapy, chemotherapy, and low accessibility to tumor tissues. Developing novel strategies to minimize adverse side effects, improve chemotherapy sensitivity, and control cancer progression is needed. Many studies have suggested small dietary molecules as complementary treatments for cancer patients. Different components of herbal/edible plants, known as flavonoids, have recently garnered attention due to their broad biological properties (e.g., antioxidant, antiviral, antimicrobial, anti-inflammatory, anti-mutagenic, anticancer, hepatoprotective, and cardioprotective). These flavonoids have shown anticancer activity by affecting different signaling cascades. This article summarizes the key progress made in this area and discusses the role of flavonoids by specifically inhibiting the PI3K/Akt/mTOR pathway in various cancers.

The Potential of Epigallocatechin Gallate (EGCG) in Targeting Autophagy for Cancer Treatment: A Narrative Review

“…Correspondingly, Hsieh et al demonstrate that, in PANC-1 cells, EGCG treatment reduces Akt phosphorylation, suggesting that the downregulation of p-Akt is associated to cytotoxic autophagy induction [ 80 ]. These findings are consistent with the literature on PI3K/Akt/mTOR signaling pathway as a “hot spot” target for anti-cancer flavonoids [ 28 ].…”

“…In response to extracellular signals, PI3K/Akt transduction regulates protein synthesis and cell growth by mTOR complex 1 (mTORC1) activation, and it inhibits apoptosis by blocking the function of pro-apoptotic Bcl-2 proteins. The activity of the kinase mammalian target of rapamycin (mTOR), a core component of mTORC1, turns out to be frequently activated in tumors, and is also a key regulator of autophagy [ 26 , 27 , 28 , 29 ]. In fact, over-activation of the PI3K-Akt pathway can result in abnormal cell proliferation, by promoting gene transcription and protein synthesis through the activation of different targets, including eukaryotic translation initiation factor 4E (eIF-4E) and S6 kinase (S6K) [ 30 ].…”

The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer

“…As compared with the high cost and side effects of most modern drugs, medical plants have shown significant therapeutic potential with minimal side effects and low cost, such as epigallocatechin gallate (EGCG), resveratrol, curcumin, sugiol etc. EGCG is a polyphenol found in green tea [ 15 , 16 , 17 , 18 ].…”

Target‐based virtual screening, computational multiscoring docking and molecular dynamics simulation of small molecules as promising drug candidate affecting kinesin‐like protein KIFC1

“…Under normal circumstances, the production of the new cells maintains equilibrium but occasionally, cells arise that no longer respond to the tightly controlled cell cycle and checkpoints. These cells give rise to clones of cells that can expand to a considerable size, producing tumour or neoplasm characterized by various salient features namely, loss of cell cycle control, heritability, transplant ability, genetic mutability, loss of density‐dependent inhibition, angiogenesis, invasiveness and metastasis 1–7 . About 10 million people succumbed to cancer in 2020 worldwide, and these data have been grown by leaps and bounds in recent years, devastating socioeconomic impact, especially in low‐and middle‐income countries.…”

“…These cells give rise to clones of cells that can expand to a considerable size, producing tumour or neoplasm characterized by various salient features namely, loss of cell cycle control, heritability, transplant ability, genetic mutability, loss of density-dependent inhibition, angiogenesis, invasiveness and metastasis. [1][2][3][4][5][6][7] About 10 million people succumbed to cancer in 2020 worldwide, and these data have been grown by leaps and bounds in recent years, devastating socioeconomic impact, especially in low-and middle-income countries. Breast cancer ranks first in new cases, followed by lung, colon and rectum, prostate, skin and stomach in 2020 (Figure 1).…”