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

• Published in: The EPMA journal 2021-12, Vol.12 (4), p.559-587
• Main Authors: Kubatka, Peter, Mazurakova, Alena, Samec, Marek, Koklesova, Lenka, Zhai, Kevin, AL-Ishaq, Raghad, Kajo, Karol, Biringer, Kamil, Vybohova, Desanka, Brockmueller, Aranka, Pec, Martin, Shakibaei, Mehdi, Giordano, Frank A., Büsselberg, Dietrich, Golubnitschaja, Olga
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer; Development and progression; DNA damage; DNA repair; Flavonoids; Gene expression; Gene mutations; Inflammation; Isoflavones; Medicine/Public Health; Metastasis; Prevention; Protein biosynthesis; Review
• ISSN: 1878-5077; 1878-5085
• DOI: 10.1007/s13167-021-00257-y

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.