Modulation of MnSOD in Cancer:Epidemiological and Experimental Evidence

Overview

Journal Toxicol Res

Specialty Toxicology

Date 2013 Nov 27

PMID 24278510

Citations 10

Authors

Aekyong Kim

Affiliations

Soon will be listed here.

Abstract

Since it was first observed in late 1970s that human cancers often had decreased manganese superoxide dismutase (MnSOD) protein expression and activity, extensive studies have been conducted to verify the association between MnSOD and cancer. Significance of MnSOD as a primary mitochondrial antioxidant enzyme is unquestionable; results from in vitro, in vivo and epidemiological studies are in harmony. On the contrary, studies regarding roles of MnSOD in cancer often report conflicting results. Although putative mechanisms have been proposed to explain how MnSOD regulates cellular proliferation, these mechanisms are not capitulated in epidemiological studies. This review discusses most recent epidemiological and experimental studies that examined the association between MnSOD and cancer, and describes emerging hypotheses of MnSOD as a mitochondrial redox regulatory enzyme and of how altered mitochondrial redox may affect physiology of normal as well as cancer cells.

Citing Articles

Recent research progress on metal ions and metal-based nanomaterials in tumor therapy.

Xu Y, Reheman A, Feng W Front Bioeng Biotechnol. 2025; 13:1550089.

PMID: 39991139 PMC: 11842396. DOI: 10.3389/fbioe.2025.1550089.

Assessment of the Impact of Trace Essential Metals on Cancer Development.

Gorska A, Markiewicz-Gospodarek A, Trubalski M, Zerebiec M, Poleszak J, Markiewicz R Int J Mol Sci. 2024; 25(13).

PMID: 38999951 PMC: 11241304. DOI: 10.3390/ijms25136842.

Insights into Manganese Superoxide Dismutase and Human Diseases.

Liu M, Sun X, Chen B, Dai R, Xi Z, Xu H Int J Mol Sci. 2022; 23(24).

PMID: 36555531 PMC: 9786916. DOI: 10.3390/ijms232415893.

The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants.

Zahra K, Lefter R, Ali A, Abdellah E, Trus C, Ciobica A Oxid Med Cell Longev. 2021; 2021:9965916.

PMID: 34394838 PMC: 8360750. DOI: 10.1155/2021/9965916.

GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms.

Ward L, Tu H, Quenneville C, Tsour S, Flynn-Carroll A, Parker M Nat Commun. 2021; 12(1):4571.

PMID: 34315874 PMC: 8316433. DOI: 10.1038/s41467-021-24563-1.

References

Schafer F, Buettner G . Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001; 30(11):1191-212. DOI: 10.1016/s0891-5849(01)00480-4. View

Hernandez-Saavedra D, McCord J . Paradoxical effects of thiol reagents on Jurkat cells and a new thiol-sensitive mutant form of human mitochondrial superoxide dismutase. Cancer Res. 2003; 63(1):159-63. View

Xu Y, Krishnan A, Wan X, Majima H, Yeh C, Ludewig G . Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells. Oncogene. 1999; 18(1):93-102. DOI: 10.1038/sj.onc.1202265. View

Kops G, Dansen T, Polderman P, Saarloos I, Wirtz K, Coffer P . Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature. 2002; 419(6904):316-21. DOI: 10.1038/nature01036. View

Ho Y, Crapo J . Isolation and characterization of complementary DNAs encoding human manganese-containing superoxide dismutase. FEBS Lett. 1988; 229(2):256-60. DOI: 10.1016/0014-5793(88)81136-0. View

Connor K, Hempel N, Nelson K, Dabiri G, Gamarra A, Belarmino J . Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res. 2007; 67(21):10260-7. DOI: 10.1158/0008-5472.CAN-07-1204. View

Li S, Yan T, Yang J, Oberley T, Oberley L . The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Cancer Res. 2000; 60(14):3927-39. View

Klaunig J, Kamendulis L, Hocevar B . Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2009; 38(1):96-109. DOI: 10.1177/0192623309356453. View

Cai Q, Shu X, Wen W, Cheng J, Dai Q, Gao Y . Genetic polymorphism in the manganese superoxide dismutase gene, antioxidant intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Breast Cancer Res. 2004; 6(6):R647-55. PMC: 1064076. DOI: 10.1186/bcr929. View

10.

Li N, Oberley T . Modulation of antioxidant enzymes, reactive oxygen species, and glutathione levels in manganese superoxide dismutase-overexpressing NIH/3T3 fibroblasts during the cell cycle. J Cell Physiol. 1998; 177(1):148-60. DOI: 10.1002/(SICI)1097-4652(199810)177:1<148::AID-JCP16>3.0.CO;2-9. View

11.

Hopper R, Carroll S, Aponte A, Johnson D, French S, Shen R . Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. Biochemistry. 2006; 45(8):2524-36. PMC: 1415274. DOI: 10.1021/bi052475e. View

12.

Kim A, Zhong W, Oberley T . Reversible modulation of cell cycle kinetics in NIH/3T3 mouse fibroblasts by inducible overexpression of mitochondrial manganese superoxide dismutase. Antioxid Redox Signal. 2004; 6(3):489-500. DOI: 10.1089/152308604773934251. View

13.

Buettner G, Ng C, Wang M, Rodgers V, Schafer F . A new paradigm: manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. Free Radic Biol Med. 2006; 41(8):1338-50. PMC: 2443724. DOI: 10.1016/j.freeradbiomed.2006.07.015. View

14.

Grasbon-Frodl E, Kosel S, Riess O, Muller U, Mehraein P, Graeber M . Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superoxide dismutase gene in German Parkinson disease patients. Biochem Biophys Res Commun. 1999; 255(3):749-52. DOI: 10.1006/bbrc.1998.9998. View

15.

Woodson K, Tangrea J, Lehman T, Modali R, Taylor K, Snyder K . Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). Cancer Causes Control. 2003; 14(6):513-8. DOI: 10.1023/a:1024840823328. View

16.

Zhao Y, Xue Y, Oberley T, Kiningham K, Lin S, Yen H . Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Cancer Res. 2001; 61(16):6082-8. View

17.

Kang D, Lee K, Park S, Berndt S, Peters U, Reding D . Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. Cancer Epidemiol Biomarkers Prev. 2007; 16(8):1581-6. DOI: 10.1158/1055-9965.EPI-07-0160. View

18.

Lin P, Hsueh Y, Ko J, Liang Y, Tsai K, Chen C . Analysis of NQO1, GSTP1, and MnSOD genetic polymorphisms on lung cancer risk in Taiwan. Lung Cancer. 2003; 40(2):123-9. DOI: 10.1016/s0169-5002(03)00027-8. View

19.

Li H, Kantoff P, Giovannucci E, Leitzmann M, Gaziano J, Stampfer M . Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. Cancer Res. 2005; 65(6):2498-504. DOI: 10.1158/0008-5472.CAN-04-3535. View

20.

Buettner G, Jurkiewicz B . Ascorbate free radical as a marker of oxidative stress: an EPR study. Free Radic Biol Med. 1993; 14(1):49-55. DOI: 10.1016/0891-5849(93)90508-r. View