To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

“…Genes regulated by NF-kB that suppress apoptosis, such as Bcl-2 and Bcl-xL (see Figure 1), are often expressed in human cancers. Given the strong association between NF-kB and the regulation of apoptosis (Burstein and Duckett, 2003;Kucharczak et al, 2003;Dutta et al, 2006), it is not surprising that many studies suggest that NF-kB controls the antiapoptotic mechanisms associated with oncogenesis. Experiments revealed that induction of expression of H-RasV12 in immortalized mouse fibroblasts leads to cellular transformation but not to apoptosis, and inhibition of NF-kB in H-RasV12-transformed cells by the expression of a 'super-repressor' degradation-resistant form of IkBa (IkBa-SR) is associated with high levels of apoptosis (Mayo et al, 1997;Baldwin, 2001), indicating that NF-kB provides a prosurvival function in the context of Ras-induced oncogenesis.…”

NF-κB meets ROS: an ‘iron-ic’ encounter

“…[1][2][3] This pathway is also crucial for pathogenesis of human diseases such as cancer and chronic inflammatory conditions, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). 1,3,4 Not surprisingly, it has been the subject of intense investigation for over one century. 1 TNFa-induced killing is antagonized by activation of NF-kB-family transcription factors 3,4 -which act as master coordinators of immune and inflammatory responses.…”

“…1 TNFa-induced killing is antagonized by activation of NF-kB-family transcription factors 3,4 -which act as master coordinators of immune and inflammatory responses. 4 The prosurvival activity of NF-kB is also crucial for lymphocyte development, tumorigenesis and cancer chemoresistance. 4,5 In recent years, remarkable progress has been made in our understanding of the mechanisms governing TNFa-induced death and NF-kB-mediated survival.…”

“…4 The prosurvival activity of NF-kB is also crucial for lymphocyte development, tumorigenesis and cancer chemoresistance. 4,5 In recent years, remarkable progress has been made in our understanding of the mechanisms governing TNFa-induced death and NF-kB-mediated survival. 3,4 As it turns out, ROS have now taken center stage in the intricate multitude of players that control cell fate downstream of TNF-R1, as they appear to be at an obligatory crossroads of the opposing pathways for life and death elicited by stimulation of this receptor.…”

Resveratrol: A miraculous natural compound for diseases treatment

“…Modulation of detoxifying enzymes (CYPs) (Baur & Sinclair, 2006), inhibition of protein kinase C (PKC) (Subbaramaiah et al., 1998), BCL‐2 (Kalra et al., 2008), and cell cycle regulators (Reagan‐Shaw, Afaq, Aziz, & Ahmad, 2004) are other chemoprevention effects of RSV. Overall, a myriad of studies has shown that several signaling pathways and various RSV targets including CD95 (Gao et al., 2002; Wenzel, Soldo, Erbersdobler, & Somoza, 2005), NF‐κβ (Li et al., 2010), Wnt (Parekh, Motiwale, Naik, & Rao, 2011), SIRT‐1, and PI3K/AKt (Kucharczak, Simmons, Fan, & Gélinas, 2003) involved in RSV‐induced anticancer effects. Tumor infraction and angiogenesis suppression are strategies against cancer spreading.…”