Abstract
Simple SummaryThere is no doubt that the need for new effective methods of cancer treatment remains challenging, as cancer is the second cause of death based on the number of cases in the world. In this review, we investigated the role of one of the leading determinants in the development and progression of various types of cancer—oxidative stress and inflammation, as well as clinical and experimental data from the studies of promising drugs of natural origin, such as flavonoids, that target these stages of oncogenesis. This can all help in the expansion and systematization of the existing knowledge regarding the fight against cancer, the facilitation of the development of effective anti-cancer drugs, and the progression of research in this field, in order to improve the treatment of these disorders.Chronic inflammation and oxidative stress are the interconnected pathological processes, which lead to cancer initiation and progression. The growing level of oxidative and inflammatory damage was shown to increase cancer severity and contribute to tumor spread. The overproduction of reactive oxygen species (ROS), which is associated with the reduced capacity of the endogenous cell defense mechanisms and/or metabolic imbalance, is the main contributor to oxidative stress. An abnormal level of ROS was defined as a predisposing factor for the cell transformation that could trigger pro-oncogenic signaling pathways, induce changes in gene expression, and facilitate accumulation of mutations, DNA damage, and genomic instability. Additionally, the activation of transcription factors caused by a prolonged oxidative stress, including NF-κB, p53, HIF1α, etc., leads to the expression of several genes responsible for inflammation. The resulting hyperactivation of inflammatory mediators, including TNFα, TGF-β, interleukins, and prostaglandins can contribute to the development of neoplasia. Pro-inflammatory cytokines were shown to trigger adaptive reactions and the acquisition of resistance by tumor cells to apoptosis, while promoting proliferation, invasion, and angiogenesis. Moreover, the chronic inflammatory response leads to the excessive production of free radicals, which further aggravate the initiated reactions. This review summarizes the recent data and progress in the discovery of mechanisms that associate oxidative stress and chronic inflammation with cancer onset and metastasis. In addition, the review provides insights for the development of therapeutic approaches and the discovery of natural substances that will be able to simultaneously inhibit several key oncological and inflammation-related targets.
Highlights
The treatment of cancer has originated from the 17th century [1] and includes a great amount of chemotherapy [2–4], radiotherapy [5–7], and surgical [8] methods
At the start of the XIX century, a relationship between cancer and the inflammatory cascade has been suggested based on observations that inflammatory cells were present in biopsy tumor samples, which often occurred in chronic inflammation sites [190]
Modern data confirm the key role of oxidative stress and chronic inflammation in various stages of tumor development: from initiation to metastasis and the formation of therapeutic resistance
Summary
The treatment of cancer has originated from the 17th century [1] and includes a great amount of chemotherapy [2–4], radiotherapy [5–7], and surgical [8] methods. Oxidative stress is an imbalance between the formed reactive oxygen species and other highly reactive compounds and antioxidants, which leads to the disruption of redox processes and control and/or molecular damage with insufficient functioning of the antioxidant system [26,27]. Oxidative stress occurs as a result of ROS, RNS, and RClS overproduction, as well as a decrease in the cell antioxidant capacity This is in turn accompanied by a number of negative effects due to the imbalance between the hyperproduction of free radicals and a decrease in the amount of antioxidant molecules [28]. Damage to the cell membrane due to lipid peroxidation can permanently impair the membrane fluidity and elasticity, which leads to cell rupture Proteins are another major target for free radical attack. FigureF2ig. uCroen2s. eCqounesneqcuesenocfetshoef rtehaecrteivacetiovxeyogxeyngesnpespcieecsieascaticotinonininththeecceelllldduurriinngg ooxxiiddaattiivveesstrtreesss.s.HHypyepreprrpordoudcuticotnioonf roefarce- active oxygentivsepoecxiyegsednisspruecpietss dthiserucepltlsftuhneccteilolnfuinngctiboynipnegrbsiystpeenrtsiostxeindtaotixvideadtiavme dagame atogelitpoidlips,idnsu, cnluecicleaicciadcisd, sa,nadndpproroteteininssdduuee to the to the disruption of various links in the functioning of these macromolecules. disruption of various links in the functioning of these macromolecules
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