Dietary Flavonoids in p53—Mediated Immune Dysfunctions Linking to Cancer Prevention

Abstract

The p53 protein plays a central role in mediating immune functioning and determines the fate of the cells. Its role as a tumor suppressor, and in transcriptional regulation and cytokine activity under stress conditions, is well defined. The wild type (WT) p53 functions as a guardian for the genome, while the mutant p53 has oncogenic roles. One of the ways that p53 combats carcinogenesis is by reducing inflammation. WT p53 functions as an anti-inflammatory molecule via cross-talk activity with multiple immunological pathways, such as the major histocompatibility complex I (MHCI) associated pathway, toll-like receptors (TLRs), and immune checkpoints. Due to the multifarious roles of p53 in cancer, it is a potent target for cancer immunotherapy. Plant flavonoids have been gaining recognition over the last two decades to use as a potential therapeutic regimen in ameliorating diseases. Recent studies have shown the ability of flavonoids to suppress chronic inflammation, specifically by modulating p53 responses. Further, the anti-oxidant Keap1/Nrf2/ARE pathway could play a crucial role in mitigating oxidative stress, leading to a reduction of chronic inflammation linked to the prevention of cancer. This review aims to discuss the pharmacological properties of plant flavonoids in response to various oxidative stresses and immune dysfunctions and analyzes the cross-talk between flavonoid-rich dietary intake for potential disease prevention.

Role of Dietary Antioxidants in p53‐Mediated Cancer Chemoprevention and Tumor Suppression

“…Phosphorylation. Phosphorylation responses to DNA damage and other stresses are controlled by regulators, subcellular localization, stability, and transcriptional activation of target genes, which prompts the biological effects [116,117]. Several kinases target specific serine and threonine residues within p53 for phosphorylation [118].…”

“…Flavonoids. Flavonoids are suggested to reduce p53mediated chronic inflammation leading to cancer progression [161]. Quercetin can induce phosphorylation of ATM and phosphorylation of histone H2AX; therefore, p53 accumulation and phosphorylation occurred in ATM-deficient cells, indicating that ATM is not required for quercetininduced p53 phosphorylation [162].…”

Biomedical Properties of Propolis on Diverse Chronic Diseases and Its Potential Applications and Health Benefits

“…The studies carried out with propolis from Asia showed that apoptosis by the mitochondrial pathway and the regulation of p53 could be the mechanism through which cell death is promoted by the extracts. Reports stated that some of the compounds commonly found in propolis are capable of regulating p53 [ 174 ]. This is promising for investigating the mechanisms of action of propolis in different types of cancer, so we think that it is necessary to replicate these studies using different cell lines and studies with 3D cultures.…”

Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells

“…p53 is another key mediator that switches its functions between DNA repair and/or cell death upon cellular stress/stimulus (Siddiqui et al, 2020). We observed an upregulated p‐p53 level in MCF‐7 cells, while a mutant p53 remained unchanged in MDA‐MB‐231 cells.…”

“…ATM‐Chk2 and ATR‐Chk1 pathways are well established upon stress conditions, a process regulated by the p53 tumor suppressor gene (Ou, Chung, Sun, & Shieh, 2005; Ramadan et al, 2020). p53 regulates apoptosis by activating DNA damage response (DDR) mechanisms in response to an external stimuli/stress and/or initiates the DNA repair process if the damage level is repairable (Siddiqui, Rahman, Rupasinghe, & Vazhappilly, 2020). Studies have shown that the p53 activation also initiates a downstream cascade, p21‐mediated cell cycle arrest in breast cancer cells (Shamloo & Usluer, 2019).…”