Oxidative stress, inflammation, and cancer: How are they linked?
Publication Date:
Accepted 3 September 2010 Available online 16 September 2010
Article Source:
sent to me by Dr. Aggarwal
Article Source Type:
pdf 
Extensive research during the past 2 decades has revealed the mechanism by which continued oxidative
stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer,
diabetes, and cardiovascular, neurological, and pulmonary diseases. Oxidative stress can activate a variety of
transcription factors including NF-κB, AP-1, p53, HIF-1α, PPAR-γ, β-catenin/Wnt, and Nrf2. Activation of these
transcription factors can lead to the expression of over 500 different genes, including those for growth factors,
inflammatory cytokines, chemokines, cell cycle regulatory molecules, and anti-inflammatory molecules. How
oxidative stress activates inflammatory pathways leading to transformation of a normal cell to tumor cell,
tumor cell survival, proliferation, chemoresistance, radioresistance, invasion, angiogenesis, and stem cell
survival is the focus of this review. Overall, observations to date suggest that oxidative stress, chronic
inflammation, and cancer are closely linked.
Conclusion
This review clearly implicates the role of ROS in various phases of
tumorigenesis. Therefore, targeting redox-sensitive pathways and
transcription factors offers great promise for cancer prevention and
therapy. Numerous agents that can interfere with redox cell signaling
pathways have been identified [9,312,313]. These include nutraceuticals
derived from fruits, vegetables, spices, grains, and cereals. They
have been shown to suppress tumorigenesis in preclinical models.
Whether these agents can inhibit tumor growth in patients remains to
be elucidated.
To read the entire article-
Chronic Inflammation and Cancer: The Role of the Mitochondria
"ABSTRACT: Accumulating evidence shows that chronic inflammation can promote all stages of tumorigenesis, including DNA damage, limitless replication, apoptosis evasion, sustained angiogenesis, self-sufficiency in growth signaling, insensitivity to anti-growth signaling, and tissue invasion/metastasis. Chronic inflammation is triggered by environmental (extrinsic) factors (eg, infection, tobacco, asbestos) and host mutations (intrinsic) factors (eg, Ras, Myc, p53). Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation. However, the precise molecular mechanisms involved and the interconnecting crosstalk between pathways remain incompletely understood. We review the evidence implicating a strong association between chronic inflammation and cancer, with an emphasis on colorectal and lung cancer. We summarize the current knowledge of the important molecular and cellular pathways linking chronic inflammation to tumorigenesis. Specifically, we focus on the role of the mitochondria in coordinating life- and death-signaling pathways crucial in cancer- related inflammation. Activation of Ras, Myc, and p53 cause mitochondrial dysfunction, resulting in mitochondrial reactive oxygen species (ROS) production and downstream signaling (eg, NFκB, STAT3, etc.) that promote inflammation- associated cancer. A recent murine transgenic study established that mitochondrial metabolism and ROS production are necessary for K-Ras–induced tumorigenicity. Collectively, inflammation-associated cancers resulting from signaling pathways coordinated at the mitochondrial level are being identified that may prove useful for developing innovative strategies for both cancer prevention and cancer treatment...
Conclusions
Cancer-related inflammation remains a significant challenge to healthcare providers, as well as to investigators studying the basic mechanisms underlying tumorigenesis. Largely because the pathogenesis of inflammation-associated cancer is incompletely understood, there are currently limited therapeutic techniques for modifying cancers that occur in the setting of chronic inflammation. The accumulating evidence links a wide variety of chronic inflammatory conditions to diverse groups of cancers (see Table 1), providing firm support for the role of inflammation-associated cancer as an important event in the pathogenesis of cancer. It may even be the seventh hallmark of cancer, as suggested by Mantovani et al.[4] In this review, we summarized the evidence implicating a growing number of key molecular and cellular pathways mediating cancers that occur in the setting of chronic inflammation (see Figure). In particular, we reviewed current knowledge implicating the mitochondria, especially mitochondrial ROS, as a central regulator in inflammation-associated cancer. As summarized in Table 2, there is much that we know about what promotes inflammation-associated cancer, but there remain a number of crucial missing pieces of experimental evidence that will be necessary to definitively prove a causal relationship between inflammation and cancer. In this regard, future in vivo studies utilizing novel targeted murine transgenic approaches, such as those described herein, will be necessary to advance our understanding of the field. Strategies aimed at enhancing mitochondrial DNA integrity and/or increasing mitochondrial antioxidant defenses may prove beneficial in reducing malignant transformation after exposure to noxious agents (eg, tobacco, PM) and host mutations that result in inflammation-associated cancer. Importantly, the significance of these investigations is that they provide the molecular rationale for developing urgently needed and novel strategies for cancer prevention and treatment."
To read the entire article-
http://www.cancernetwork.com/display/article/10165
/1842753?GUID=B0BDB0DD-77D5-4084-81FB-5DDBABF67E83&
David Emerson
Bookmark/Search this post with:
