Superoxide dismutases in the human colorectal cancer sequence

Janssen, A. Miranda L.; Bosman, C; Kruidenier, Laurens; Griffioen, G.; Lamers, C. B. H. W.; Krieken, J. Han J.M. van; Velde, C. J. H. van de; Verspaget, Hein W.

doi:10.1007/s004320050282

Cited by 70 publications

(57 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were observed in our preliminary research (31), and these data are comparable to other studies in human colorectal (32) and in esophageal and gastric cancer which showed also a significant TNF-· increase (33). In this regard, MnSOD is characterized by low expression levels in cells, but can be strongly induced both in vivo and in vitro by multiple stress conditions, such as the presence of cytokines (such as TNF-· and interleukin-1), changes in cell redox state and hyperoxia (24).…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Implications of antioxidant enzymes in human gastric neoplasms

Monari¹

2009

Int J Mol Med

View full text Add to dashboard Cite

Abstract. The present study is the first to evaluate the expression and activity of MnSOD, Cu/ZnSOD and catalase in human gastric samples, since ROS play a significant role in the pathogenesis of different forms of malignancy inducing mutations and various diseases such as gastric cancer. Biopsies and surgical samples from 53 patients (male/female 22/31, mean age 56.5±15.8 years) consisted of 15 healthy, 12 autoimmune atrophic gastritis, 10 Helicobacter pylori (HP) infection, 8 HP-negative chronic gastritis (CG) and 8 adenocarcinoma cases. Enzyme activity and expression were evaluated by spectrophotometry and immunoblotting after specific extraction in phosphate buffer. We found that MnSOD activity was increased in adenocarcinoma, CG and HP tissues (p<0.05-0.001), while Cu/ZnSOD was significantly lower in adenocarcinoma and HP tissues (p<0.001) when compared to the healthy control. MnSOD and Cu/ZnSOD were expressed to a significantly higher degree in adenocarcinoma and HP tissues (p<0.05 and <0.001 respectively) and to a significantly lower degree in CG tissues with respect to the healthy patients (p<0.05 and <0.001). A significant decrease in CAT activity in adenocarcinoma and HP tissues was observed (p<0.01 and <0.05). Gastric human neoplasms showed significant changes in antioxidant enzymes, that represent the first line in antioxidant protection against radical attack. The difficulties in correlating the antioxidant enzyme with the neoplasms was related to the complexity of the biochemical pathways that regulate the cellular redox balance. Our results are important in enhancing the understanding of the role that these enzymes play in the promotion/ suppression of the carcinogenesis cascade in human gastric mucosa.

show abstract

Section: Discussionsupporting

confidence: 93%

“…Furthermore, low levels of Cu/ZnSOD were found in undifferentiated colorectal cancer when compared with moderately or well differentiated carcinomas, without a specific ratio between MnSOD and Cu/ZnSOD (32).…”

Section: Discussionmentioning

confidence: 92%

Implications of antioxidant enzymes in human gastric neoplasms

Monari¹

2009

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Reduction of sensitivity to radiation therapy has also been implied as the mechanism that sustains the role as negative prognostic factor of MnSOD for local recurrence of cervical carcinomas (Nakano et al, 1996). The possibility that an increase of MnSOD level is a relatively late event that boosts the malignant potency of tumours was already suggested by our data and is further supported by the work of Lam et al (1999) showing that over-expression of MnSOD results in increase of cell invasiveness in hamster cheek pouch carcinoma cells, and by data reported by Janssen et al (1999), showing that neoplastic epithelial cells and metastasis of colon carcinomas had levels of this enzyme higher than intermediate dysplastic adenoma cells.…”

supporting

confidence: 83%

The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications

et al. 2001

View full text Add to dashboard Cite

SummaryWe address the issue of the role of manganese superoxide dismutase in tumorigenesis by studying a relatively homogeneous group of tumours for the correlation between amount of this anti-oxidant enzyme and prognosis. The clinical outcome of 30 patients affected by glioblastomas whose manganese superoxide dismutase content had been established at the time of first diagnosis is compared. When the survival of patients is stratified according to manganese superoxide dismutase level in the tumour, a link of these levels and prognosis can be observed. Patients with high levels of manganese superoxide dismutase show a median survival time of 6.11 months, while patients whose tumours display a low amount of MnSOD have a median survival time of 12.17 months. To assess the upstream mechanisms that sustain the increase in manganese superoxide dismutase content in brain neuroepithelial tumours, we also studied the expression of p53 in a series of 17 astrocytomas of various grading. In all tested astrocytomas, high manganese superoxide dismutase content is associated with cytoplasmic accumulation of p53. Thus glioblastomas can be divided into two distinct groups on the basis of their content of manganese superoxide dismutase, having 'better' or 'worse' prognosis, respectively. The use of this protein as a marker may help to define therapeutic strategies in the clinical management of glioblastoma.

show abstract

“…Indeed, most cells have abundant Cu/Zn-SOD and glutathione peroxidase (Gpx) to dismutate ROS into molecular oxygen and water, making an anti-cancer mechanism of rMnSOD questionable. Moreover, previous studies showed increased levels of both Zn/Cu-SOD and MnSOD in cancer cells of various tissue origins whereas high levels of MnSOD expression [29][30][31] have been detected in various primary human cancer tissues and in blood samples from patients with various types of leukaemia. 32 However, as MnSOD levels seem to decrease in certain cancer cells and forced expression of MnSOD appears to suppress malignant phenotypes in certain experimental models, only MnSOD, and not Zn/Cu-SOD, was considered as a tumour suppressor protein.…”

Section: Discussionmentioning

confidence: 99%

Biophysical and biochemical characterization of a liposarcoma‐derived recombinant MnSOD protein acting as an anticancer agent

Mancini¹,

Borrelli²,

Schiattarella³

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68 Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125 I-and 131 I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism. '

show abstract

Superoxide dismutases in the human colorectal cancer sequence

Abstract: Our study indicates that the development of neoplasia in the human colorectum is accompanied by major changes in the level and activity of Mn-SOD. This observation illustrates that Mn-SOD might have a functional role in human colorectal carcinogenesis.

Cited by 70 publications

References 50 publications

Implications of antioxidant enzymes in human gastric neoplasms

Implications of antioxidant enzymes in human gastric neoplasms

The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications

Biophysical and biochemical characterization of a liposarcoma‐derived recombinant MnSOD protein acting as an anticancer agent

Contact Info

Product

Resources

About