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Opinion Volume 4 Issue 1
ROS induced inflammation is key driver of afb1 induced hepatocellular carcinoma
Brajesh Kumar Maurya
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Department of Zoology, Govt. PG College Obra Sonebhadra- Uttar Pradesh, India
Correspondence: Brajesh Kumar Maurya, HOD, Department of Zoology, Govt. PG College Obra Sonebhadra-231219 Uttar Pradesh, India, Tel 9450 061618
Received: January 29, 2018 | Published: February 12, 2018
Citation: Maurya BK. ROS induced inflammation is key driver of afb1 induced hepatocellular carcinoma. J Liver Res Disord Ther. 2018;4(1):44-45. DOI: 10.15406/jlrdt.2018.04.00095
Keywords
hepatocellular carcinoma, aflatoxin b1, reactive oxygen species, cancer related inflammation
Abbreviations
HCC, hepatocellular carcinoma; AFB1, aflatoxin B1; CRI, cancer related inflammation; NFkB, nuclear factor kappa b; TNF, tumor necrosis factor; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; DED, death effectors domain; TRADD TNF, associated death domain; cFLIP, cellular fas-assocciated death domain like interleukin-1-β converting enzyme inhibitory protein
Opinion
Reactive oxygen species and inflammation are known to promote tumor progression.1 ROS causes genomic instability and necrotic cell death2 this in turn, may induce production of pro-inflammatory factors resulting into neoplastic progression in case of many cancers.3,4 It has been observed that AFB1 also induces necrotic cell deaths in the liver to drive hepatocarcinogenesis.4 Thereby, it is hypothesized that AFB1 induced HCC might involve ROS led, inflammatory cascades during hepatocarcinogenesis (Figure).
Figure 1 ROS and inflammation drive progression of AFB1 induced carcinogensis.
Based on the findings during recent past, it is assumed that cancer related inflammation (CRI) could be considered as another hallmark of cancers5 because this event is found to be shared by almost all types of cancers.6 Among inflammatory factors of the CRI; IL-1α, IL-1β and TNFα are considered to be of much importance. This is because; they implicate NFκB dependent expression of many cell proliferative factors.7 IL-1α activates the nearby inflammatory cells and thereby, provokes NFκB dependent production of a battery of tumorigenic factors.1,7 In addition, TNFα signaling also results into translocation of NFκB into the nucleus, which in turn induces expression of certain inflammation supportive factors like; Bcl2, COX-2, iNOS and IL-1β, which are known to support tumor growth also.7
TNFα signaling is evident to be critically implicated in tumor progression.8 This involves competitive interaction of TRADD vs cFLIP with TNF-R cytosolic domain9,102010. Several mutations in TRADD and cFLIP in breast cancer, cervical cancer and HCC cell lines have been reported to enhance the binding of cFLIP to DED domain of TNFα-R and thereby promoting cell survival over induction of apoptosis in these cells.10 Thus, altered ratio of TRADD vs CFLIP is considered to be critical during TNFα signaling induced tumorigenic progression.
In this context, TNFα-activated nuclear NFκB (p65) translocation into nucleus and maintenance of Bcl2 constitute a mechanism of driving the cells in proliferation pathway.7 In addition, Expression of NFκB dependent genes like COX-2 and iNOS are also found to be critically involved in inflammation induced tumor development. However, whether this mechanism is involved in AFB1 induced HCC development remains unexplored.
Acknowledgements
None.
Conflict of interest
Author declares that there is no conflict of interest.
References
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- Bagnoli M, Canevari S, Mezzanzanica D. Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol. 2010;42(2):210‒213.
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