Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression—3PM pathways

Abstract

Inflammation is an essential pillar of the immune defense. On the other hand, chronic inflammation is considered a hallmark of cancer initiation and progression. Chronic inflammation demonstrates a potential to induce complex changes at molecular, cellular, and organ levels including but not restricted to the stagnation and impairment of healing processes, uncontrolled production of aggressive ROS/RNS, triggered DNA mutations and damage, compromised efficacy of the DNA repair machinery, significantly upregulated cytokine/chemokine release and associated patho-physiologic protein synthesis, activated signaling pathways involved in carcinogenesis and tumor progression, abnormal tissue remodeling, and created pre-metastatic niches, among others. The anti-inflammatory activities of flavonoids demonstrate clinically relevant potential as preventive and therapeutic agents to improve individual outcomes in diseases linked to the low-grade systemic and chronic inflammation, including cancers. To this end, flavonoids are potent modulators of pro-inflammatory gene expression being, therefore, of great interest as agents selectively suppressing molecular targets within pro-inflammatory pathways. This paper provides in-depth analysis of anti-inflammatory properties of flavonoids, highlights corresponding mechanisms and targeted molecular pathways, and proposes potential treatment models for multi-level cancer prevention in the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). To this end, individualized profiling and patient stratification are essential for implementing targeted anti-inflammatory approaches. Most prominent examples are presented for the proposed application of flavonoid-conducted anti-inflammatory treatments in overall cancer management.

Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care

“…Results of experiments showed a direct association between the application of phytochemicals and the suppression of cancer development through the modulation of different cell signalling pathways [ 33 ]. Numerous phytoconstituents in function food regulate events connected with malignant transformation, such as apoptosis [ 26 ], proliferation [ 34 ], angiogenesis [ 27 ], inflammation [ 35 ], invasiveness, and metastasis [ 12 ]. Many studies described the significant role of phytochemicals in modulating epigenetic changes and metabolic reprogramming—key events for cancer initiation, promotion, and progression [ 36 , 37 ].…”

“…Despite the role of the factors on the side of the individual, the metabolism of phytochemicals is also affected by the structural complexity of phytochemicals alone [ 12 , 104 ]. However, despite the described low bioavailability and bioactivity of phytochemicals in organisms, preclinical in vivo studies demonstrate a potent anticancer efficacy of whole plant food in animal models [ 29 , 35 , 42 , 43 , 48 , 105 ]. Furthermore, some metabolites exert a better physiological function when compared with their precursor [ 12 , 106 ].…”

“…Health risk assessment followed by targeted damage-mitigating measures and protection tailored to the individualized patient profile are instrumental to reverse health damage at the level of sub-optimal health [ 120 , 121 ]. As demonstrated above, an application of phytochemicals in the framework of primary care might be a particularly cost-effective approach exemplified by the evidence-based protection against the non-physiologic inflammation [ 35 ] and mitochondrial dysfunction [ 122 ] as well as against the Warburg malignant transformation [ 38 ]. In 2018, Polivka J Jr. et al published a strategic article which later on has been distinguished by Springer-Nature as groundbreaking scientific findings that could help humanity and protect our planet in category “Medicine and Public Health”.…”

Maternal vascular status and BMI-associated phenotyping is instrumental for predictive, preventive and personalised approach in healthy pregnancy

“…Maternal in ammation could result in metabolic reprogramming at the stage of periconceptional period as well as at other stages of placental / embryonic development [72]. Naturally occurring phytochemicals exert potent anti-in ammatory effects [73]. To this end, consumption of garlic demonstrates a signi cant decrease in CRP levels as measured, for example in pregnant women at high risk for pre-eclampsia [74].…”

A Dietary Antioxidant Formulation Ameliorates DNA Damage Caused by γ-Irradiation in Normal Human Bronchial Epithelial Cells In Vitro

“…Flavonoids regulate all phases of the intricate process of carcinogenesis, which is linked to inflammation. Thus, flavonoids and other phytochemicals have been proposed to be used in the overall cancer management framework of predictive, preventive, and personalized medicine [ 25 ]. We investigated whether an antioxidant formulation called AOX2 that contains vitamin C (ascorbic acid; AA), vitamin B9 (folate), vitamin B12 (cyanocobalamin), vitamin E (α-tocopherol), α-lipoic acid, coenzyme Q10 (CoQ10), astaxanthin, zeaxanthin, quercetin (Q), and sodium selenite could help develop chemoprotective interventions for ROS-induced DNA damage caused by diagnostic scans employing ionizing radiation and smoke-related carcinogens by examining if it could protect against DNA damage caused by low-dose γ-radiation and the chemical carcinogen NNKOAc in BEAS-2B cells.…”