4.6 Review

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

期刊

EPMA JOURNAL
卷 12, 期 4, 页码 559-587

出版社

SPRINGER INT PUBL AG
DOI: 10.1007/s13167-021-00257-y

关键词

Natural substances; Phytochemicals; Flavonoids; ROS; DNA damage; Carcinogenesis; Inflammation; Low-grade systemic inflammation; Cancer; Cancer initiation; Cancer promotion; Cancer progression; Systemic hypoxic-ishemic effects; Pre-metastatic niches; Impaired healing; Molecular targets; NF-kappa B signaling; Inflammatory pathway; HIF-1 alpha; TNF-alpha; Cytokines; IL-1 beta; IL-6; IL-8; S100; Tissue remodeling; Matrix metalloproteinases; Predictive preventive personalized medicine (PPPM / 3PM)

资金

  1. Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (Bratislava, Slovak Republic) [1/0136/19]
  2. Slovak Research and Development Agency [APVV-16-0021]
  3. National Priorities Research Program [NPRP 11S-1214170101]
  4. Qatar National Research Fund
  5. LISPER project [313011V446]

向作者/读者索取更多资源

Inflammation plays a crucial role in immune defense, while chronic inflammation is considered a hallmark of cancer initiation and progression. Flavonoids, with their anti-inflammatory activities, have the potential to be preventive and therapeutic agents in diseases linked to chronic inflammation, including cancer. Individualized profiling and patient stratification are essential for implementing targeted anti-inflammatory approaches in overall cancer management.
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.

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