RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells

Holley, Aaron K.; Xu, Yong; Clair, Daret K. St.; Clair, William H. St.

doi:10.1111/j.1749-6632.2010.05613.x

Cited by 53 publications

(55 citation statements)

References 72 publications

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“…NF-κB has been linked to cell proliferation, invasion, angiogenesis, metastasis, suppression of apoptosis and chemoresistance in multiple tumors (38,39). In addition, evidence suggests that NF-κB is significant in the growth and radio/chemoresistance of prostate cancer (40)(41)(42)(43)(44). Curcumin is able to suppress NF-κB activation by an Akt-dependent or Akt-independent inhibition of IKK (15,16,45).…”

Section: Discussionmentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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Abstract. Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A 1 -A 6 ) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A 2 -A 6 ) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A 2 -A 6 also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A 2 -A 6 using suitable animal models of prostate cancer. IntroductionCurcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Curcumin lacks toxicity in humans (1), and extensive research over several decades has revealed that curcumin possesses anticancer, anti-inflammatory, antioxidant, antiviral and anti-bacterial activities (2,3). Curcumin suppressed cell proliferation or induced apoptosis in cultured prostate cancer cells and other types of cancer cells (4-10). Curcumin also inhibited prostate carcinogenesis (11). Studies from our laboratory and those of other authors have demonstrated enhanced anticancer activities of curcumin when combined with other anticancer agents (12-14). Findings of earlier studies showed that curcumin exerts a wide range of anticancer effects by modulating a diversity of signaling pathways, including nuclear factor-κB (NF-κB) and other pathways (15)(16)(17)(18)(19)(20). Curcumin has entered clinical trials for certain types of human cancer (21-23). However, the clinical efficacy of curcumin is limited, which is likely to be due to its low bioavailability (21-23). It was suggested that the β-diketone moiety of curcumin causes instability and poor metabolic properties (24-26). Enhanced stability was found in curcumin analogues by deleting the β-diketone moiety of the molecule (27). Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells. We also determined the inhibitory effect ...

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Section: Discussionmentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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“…Disruption of the ROS production/detoxification cycle, contributes to the development of human pathologies, including age-related diseases, such as cancer (58,68,80,178), cardiovascular (38,139), neurodegenerative (178), and genetic disorders (33,88). ROS can also be generated by exogenous sources like ionizing radiation (IR) (75,110), through direct interactions with either cellular targets or with water, resulting in DNA damage and gene mutations (45,69) or cell death (110). However, under oxidative stress, ROS induces the intrinsic antioxidant enzymes to protect cells from ROS-induced toxicity (64).…”

Section: Oxidative Stress and Mpimentioning

confidence: 99%

“…Studies using mice (182) and fruit flies (40) demonstrated that MnSOD gene knockout is lethal; while MnSOD heterozygous mice with haplo-insufficiency can survive but are more susceptible to oxidative injury (169,171). The crucial role of MnSOD in protecting cells against oxidative stress has been extensively studied and thoroughly reviewed (75,89,123,130,150,161), pointing to the critical roles of MnSOD in maintaining cellular physiology in response to genotoxic conditions, such as oxidative stress. In addition to MnSOD gene transcription, accumulating evidence indicates that MnSOD enzymatic activity is enhanced via post-translational modifications.…”

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confidence: 99%

MnSOD in Oxidative Stress Response-Potential RegulationviaMitochondrial Protein Influx

Candas

2014

Antioxidants & Redox Signaling

276

178

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Significance: The mitochondrial antioxidant manganese superoxide dismutase (MnSOD) is encoded by genomic DNA and its dismutase function is fully activated in the mitochondria to detoxify free radical O 2 -generated by mitochondrial respiration. Accumulating evidence shows an extensive communication between the mitochondria and cytoplasm under oxidative stress. Not only is the MnSOD gene upregulated by oxidative stress, but MnSOD activity can be enhanced via the mitochondrial protein influx (MPI). Recent Advances: A cluster of MPI containing cytoplasmic/nuclear proteins, such as cyclins, cyclin-dependent kinases, and p53 interact with and alter MnSOD activity. These proteins modulate MnSOD superoxide scavenging activity via post-translational modifications in the mitochondria. In addition to well-established pathways in gene expression, recent findings suggest that MnSOD enzymatic activity can also be enhanced by phosphorylation of specific motifs in mitochondria. This review attempts to discuss the pre-and post-translational regulation of MnSOD, and how these modifications alter MnSOD activity, which induces a cell adaptive response to oxidative stress. Critical Issues: MnSOD is biologically significant to aerobic cells. Its role in protecting the cells against the deleterious effects of reactive oxygen species is evident. However, the exact network of MnSOD-associated cellular adaptive reaction to oxidative stress and its post-translational modifications, especially its enzymatic enhancement via phosphorylation, is not yet fully understood. Future Directions: The broad discussion of the multiple aspects of MnSOD regulation, including gene expression, protein modifications, and enzymatic activity, will shed light onto the unknown mechanisms that govern the prosurvival networks involved in cellular and mitochondrial adaptive response to genotoxic environment. Antioxid. Redox Signal. 20, 1599Signal. 20, -1617

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“…The most recent studies have shown increased levels of MnSOD expression in cancer cells of various tissue origins (Hu et al, 2005), positively correlating with aggressive or metastatic stages of cancers (Malafa et al, 2000;Ennen et al, 2011). Altered transcription factor profiles in cancer cells, such as aberrant activation of NFkB (Dhar et al, 2010;Holley et al, 2010), SP-1 (Dhar et al, 2010) and inactivation of p53 (Dhar et al, 2010), are suggested to be attributable to increases in MnSOD expression.…”

Section: /2mentioning

confidence: 99%

Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration

Zhang

Wang

Liang

et al. 2014

Journal of Cell Science

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Cell migration is a dynamic process that is central to a variety of physiological functions as well as disease pathogenesis. The modulation of cell migration by p27 has been reported, but the exact mechanism(s) whereby p27 intersects with downstream effectors that control cell migration have not been elucidated. By systematically comparing p27+/+ MEFs with genetically ablated p27−/− MEFs using wound healing, transwell and time-lapse microscopic analyses, we provide direct evidence demonstrating that p27 inhibits both directional and random cell migration. Identical results were obtained with normal and cancer epithelial cells using complementary knockdown and overexpression approaches. Additional studies revealed that overexpression of manganese superoxide dismutase (MnSOD) and reduced intracellular oxidation played a key role in increased cell migration in p27-deficient cells. Furthermore, we identified signal transducer and activator of transcription 3 (STAT3) as the transcription factor responsible for p27-regulated MnSOD expression which was further mediated by ERKs/ATF1-dependent transactivation of CRE within the stat3 promoter. Collectively, our data strongly indicate that p27 plays a crucially negative role in cell migration by inhibiting MnSOD expression in a STAT-3 dependent manner.

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RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells

Cited by 53 publications

References 72 publications

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

MnSOD in Oxidative Stress Response-Potential RegulationviaMitochondrial Protein Influx

Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration

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