Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.

Abstract

Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

“…The effects of a-TOS on cancer cells, combined with a reduced toxicity towards normal cells, result from a greater antioxidant defence of the latter (Church et al, 1993;Safford et al, 1994;Allen and Balin, 2003;Huang et al, 2006) and/or increased levels of esterases that hydrolyse the pro-oxidant a-TOS by hydrolysis to the redox-active, non-apoptogenic a-TOH Neuzil and Massa, 2005).…”

All-trans-retinoic acid induces manganese superoxide dismutase in human neuroblastoma through NF-κB

“…We have previously shown that overexpression of MnSOD in a murine fibrosarcoma cell line results in a decrease in the activity of Jun associated transcription factors resulting in a subsequent downregulation of target protooncogenes [8]. Additionally, our group and others have shown that MnSOD transgenic cell lines, relative to wild-type cells, have significantly slower growth rates, decreased colony formation and exhibit morphological changes consistent with a differentiated phenotype [9][10][11][12].…”

Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells

“…Expression of the human MnSOD gene in mouse C3H10T1/2 cells enhances cellular differentiation upon treatment with 5-azacytidine . The malignant phenotype of human melanoma cells was suppressed by introduction of human chromosome 6 where the MnSOD gene is located (Trent et al, 1990) or transfection of a human MnSOD cDNA (Church et al, 1993). Overexpression of MnSOD suppressed the malignant phenotypes of human breast cancer cells (Li et al, 1995), human glioma cells (Zhong et al, 1997), and mouse epidermal cells (Amstad et al, 1997).…”