Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?

Bystrom, Laura M.; Guzmán, Mónica L.; Rivella, Stefano

doi:10.1089/ars.2012.5014

Cited by 175 publications

(137 citation statements)

References 49 publications

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“…8B). These data support the concept that moderate induction of ROS in cancer cells would contribute to cell proliferation rather than triggering cell death [42,45].…”

Section: Iron and Il-6 Jointly Promoted Tumor Cell Growthsupporting

confidence: 84%

“…S7). The tumorigenic effect of iron has been attributed to several factors, such as overproduction of ROS and free radicals through irondependent Fenton reaction, induction of oxidative responsive transcriptional factors and pro-inflammatory cytokines and iron-mediated hypoxia signaling [39][40][41][42]. Consistent with previous studies [43,44], we demonstrated that iron treatment (FAC 32 μM, similar to the mean iron concentration in our breast cancer patients) could induce about 1.9-fold increase of intracellular ROS level in MBA-MB-231 cells compared to the control (Fig.…”

Section: Iron and Il-6 Jointly Promoted Tumor Cell Growthmentioning

confidence: 99%

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Disordered hepcidin–ferroportin signaling promotes breast cancer growth

Zhang

Chen

Guo

et al. 2014

Cellular Signalling

109

136

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Iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including cancers. Burgeoning evidence indicates that the central signaling of iron homeostasis, the hepcidin-ferroportin axis, is misregulated in cancers. Nonetheless, the mechanisms of misregulated expression of iron-related genes along this signaling in cancers remain largely unknown. In the current study, we found increased levels of serum hepcidin in breast cancer patients. Reduction of hepatic hepcidin through administration of heparin restrained tumorigenic properties of breast tumor cells. Mechanistic investigation revealed that increased iron, bone morphogenetic protein-6 (BMP6) and interleukin-6 (IL-6) jointly promoted the synthesis of hepatic hepcidin. Tumor hepcidin expression was marginally increased in breast tumors relative to adjacent tissues. In contrast, tumor ferroportin concentration was greatly reduced in breast tumors, especially in malignant tumors, compared to adjacent tissues. Elevation of ferroportin concentration inhibited cell proliferation in vitro and in vivo by knocking down tumor hepcidin expression. Additionally, increased IL-6 was demonstrated to jointly enhance the tumorigenic effects of iron through enforcing cell growth. Our combined data overall deciphered the machinery that altered the hepcidin-ferroportin signaling in breast cancers. Thus, targeting the hepcidin-ferroportin signaling would represent a promising therapeutics to restrain breast cancer growth.

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“…8B). These data support the concept that moderate induction of ROS in cancer cells would contribute to cell proliferation rather than triggering cell death [42,45].…”

Section: Iron and Il-6 Jointly Promoted Tumor Cell Growthsupporting

confidence: 84%

Section: Iron and Il-6 Jointly Promoted Tumor Cell Growthmentioning

confidence: 99%

Disordered hepcidin–ferroportin signaling promotes breast cancer growth

Zhang

Chen

Guo

et al. 2014

Cellular Signalling

109

136

View full text Add to dashboard Cite

show abstract

“…Hepcidin expression is fundamentally governed by the BMP family members (Andriopoulos et al, 2009) and the IL-6 family cytokines (Banzet et al, 2012) through erythropoietic demand, iron burden and inflammatory stimuli (Ganz, 2010). Hepcidin deficiency is associated with increased serum iron and leads to a few iron-related disorders, such as nervous system diseases (Jeong and David, 2003), hepatocirrhosis (Fei et al, 2006) and even cancers (Bystrom et al, 2012;Nemeth and Ganz, 2006).…”

Section: Introductionmentioning

confidence: 99%

PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression

Wang

Zhang

Lin

et al. 2013

Gene

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a b s t r a c t a r t i c l e i n f oPCBs are a family of persistent environmental toxicants with a wide spectrum of toxic features, such as immunotoxicity, hepatoxicity, endocrine disruption effects, and oncogenic effects. To date, little has been done to investigate the potential influence of PCB exposure on iron metabolism. Deregulated iron would lead to either iron deficiency or iron excess, coupled with various diseases such as anemia or hemochromatosis. Iron metabolism is strictly governed by the hepcidin-ferroportin axis, and hepcidin is the key regulator that is secreted by hepatocytes. Here, we found that PCB-77 could go through plasma membrane and accumulate in hepatocytes. PCB-77 was demonstrated to suppress hepcidin expression in HepG2 and L-02 hepatocytes. Moreover, hepatic hepcidin was observed to be inhibited in mice upon administration of PCB-77. Due to reduced hepcidin concentration, serum iron content was increased, with a significant reduction of splenic iron content. Together, we deciphered the molecular mechanism responsible for PCB-conducted disturbance on iron homeostasis, i.e. through misregulating hepatic hepcidin expression.

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“…1), resulting in enforced iron supply to other tissues including tumors. Excessive iron availability will enhance the rate of iron-dependent biological processes necessary for cell growth, and elevate the risk of genetic mutation via free radical production (Bystrom et al, 2014;Torti and Torti, 2011). It has been suggested that excessive iron can greatly increase the incidence of various cancers and neurological diseases (Ganz and Nemeth, 2011;Zhang et al, 2014).…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

“…It has been suggested that excessive iron can greatly increase the incidence of various cancers and neurological diseases (Ganz and Nemeth, 2011;Zhang et al, 2014). Additionally, numerous studies have suggested the notable contribution of excess iron to tumor development (Bystrom et al, 2014;Richardson et al, 2009;Torti and Torti, 2011).…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%