Full Text:   <2776>

CLC number: R737.31

On-line Access: 2011-05-06

Received: 2010-05-30

Revision Accepted: 2010-09-29

Crosschecked: 2011-03-30

Cited: 6

Clicked: 6791

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.5 P.346-356


Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior

Author(s):  Yue Wang, Li Dong, Heng Cui, Dan-hua Shen, Ying Wang, Xiao-hong Chang, Tian-yun Fu, Xue Ye, Yuan-yang Yao

Affiliation(s):  Department of Obstetrics and Gynecology, People’s Hospital, Peking University, Beijing 100044, China, Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Peking University, Beijing 100035, China, Department of Pathology, People’s Hospital, Peking University, Beijing 100044, China

Corresponding email(s):   wangyue99992002@yahoo.com

Key Words:  Ovarian carcinoma, Mitochondria, Invasion, Proteomic, Superoxide dismutase 2 (SOD2)

Yue Wang, Li Dong, Heng Cui, Dan-hua Shen, Ying Wang, Xiao-hong Chang, Tian-yun Fu, Xue Ye, Yuan-yang Yao. Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior[J]. Journal of Zhejiang University Science B, 2011, 12(5): 346-356.

@article{title="Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior",
author="Yue Wang, Li Dong, Heng Cui, Dan-hua Shen, Ying Wang, Xiao-hong Chang, Tian-yun Fu, Xue Ye, Yuan-yang Yao",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior
%A Yue Wang
%A Li Dong
%A Heng Cui
%A Dan-hua Shen
%A Ying Wang
%A Xiao-hong Chang
%A Tian-yun Fu
%A Xue Ye
%A Yuan-yang Yao
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 5
%P 346-356
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000192

T1 - Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior
A1 - Yue Wang
A1 - Li Dong
A1 - Heng Cui
A1 - Dan-hua Shen
A1 - Ying Wang
A1 - Xiao-hong Chang
A1 - Tian-yun Fu
A1 - Xue Ye
A1 - Yuan-yang Yao
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 5
SP - 346
EP - 356
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000192

Objective: Recently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined. Methods: Cancer cells SKOV3.ip1 were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ip1 exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mitochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight (MALDI-TOF/TOF), and finally a selected protein candidate was further investigated by immunohistochemistry (IHC) method in nude mice bearing tumor tissues of these two cells. Results: A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis (PAGE) approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ip1 cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 (SOD2), fumarate hydratase (FH), mitochondrial ribosomal protein L38 (MRPL38), and mRNA turnover 4 homolog (MRTO4). An increased staining of SOD2 was observed in SKOV3.ip1 over that of SKOV3 in IHC analysis. Conclusions: Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Bai, F., Feng, J., Cheng, Y., Shi, J., Yang, R., Cui, H., 2006. Analysis of gene expression patterns of ovarian cancer cell lines with different metastatic potentials. Int. J. Gynecol. Cancer, 16(1):202-209.

[2]Chen, Y., McMillan-Ward, E., Kong, J., Israels, S.J., Gibson, S.B., 2007. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J. Cell Sci., 120(23):4155-4166.

[3]Connor, K.M., Subbaram, S., Regan, K.J., Nelson, K.K., Mazurkiewicz, J.E., Bartholomew, P.J., Aplin, A.E., Tai, Y.T., Aguirre-Ghiso, J., Flores, S.C., et al., 2005. Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J. Biol. Chem., 280(17):16916-16924.

[4]Connor, K.M., Hempel, N., Nelson, K.K., Dabiri, G., Gamarra, A., Belarmino, J., van de Water, L., Mian, B.M., Melendez, J.A., 2007. Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res., 67(21):10260-10267.

[5]Gottlieb, E., Tomlinson, I.P., 2005. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat. Rev. Cancer, 5(11):857-866.

[6]Heerdt, B.G., Houston, M.A., Augenlicht, L.H., 2005. The intrinsic mitochondrial membrane potential of colonic carcinoma cells is linked to the probability of tumor progression. Cancer Res., 65(21):9861-9867.

[7]Hempel, N., Ye, H., Abessi, B., Mian, B., Melendez, J.A., 2009. Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic. Biol. Med., 46(1):42-50.

[8]Hitchler, M.J., Wikainapakul, K., Yu, L., Powers, K., Attatippaholkun, W., Domann, F.E., 2006. Epigenetic regulation of manganese superoxide dismutase expression in human breast cancer cells. Epigenetics, 1(4):163-171.

[9]Hu, Y., Rosen, D.G., Zhou, Y., Feng, L., Yang, G., Liu, J., Huang, P., 2005. Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress. J. Biol. Chem., 280(47):39485-39492.

[10]Huang, X.H., Wang, Q., Chen, J.S., Fu, X.H., Chen, X.L., Chen, L.Z., Li, W., Bi, J., Zhang, L.J., Fu, Q., et al., 2009. Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatol. Res., 39(8):786-794.

[11]Hurt, E.M., Thomas, S.B., Peng, B., Farrar, W.L., 2007. Molecular consequences of SOD2 expression in epigenetically silenced pancreatic carcinoma cell lines. Br. J. Cancer, 97(8):1116-1123.

[12]Lin, Y.W., Aplan, P.D., 2007. Gene expression profiling of precursor T-cell lymphoblastic leukemia/lymphoma identifies oncogenic pathways that are potential therapeutic targets. Leukemia, 21(6):1276-1284.

[13]Naora, H., Montell, D.J., 2005. Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat. Rev. Cancer, 5(5):355-366.

[14]Nelson, K.K., Ranganathan, A.C., Mansouri, J., Rodriguez, A.M., Providence, K.M., Rutter, J.L., Pumiglia, K., Bennett, J.A., Melendez, J.A., 2003. Elevated SOD2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis. Clin. Cancer Res., 9(1):424-432.

[15]Newmeyer, D.D., Ferguson-Miller, S., 2003. Mitochondria: releasing power for life and unleashing the machineries of death. Cell, 112(4):481-490.

[16]Pani, G., Koch, O.R., Galeotti, T., 2009. The p53-p66shc-manganese superoxide dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species. Int. J. Biochem. Cell Biol., 41(5):1002-1005.

[17]Salzman, R., Kankova, K., Pacal, L., Tomandl, J., Horakova, Z., Kostrica, R., 2007. Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases. Neoplasma, 54(4):321-325.

[18]Stewart, L., Glenn, G.M., Stratton, P., Goldstein, A.M., Merino, M.J., Tucker, M.A., Linehan, W.M., Toro, J.R., 2008. Association of germline mutations in the fumarate hydratase gene and uterine fibroids in women with hereditary leiomyomatosis and renal cell cancer. Arch. Dermatol., 144(12):1584-1592.

[19]Sudarshan, S., Sourbier, C., Kong, H.S., Block, K., Valera Romero, V.A., Yang, Y., Galindo, C., Mollapour, M., Scroggins, B., Goode, N., et al., 2009. Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1α stabilization by glucose-dependent generation of reactive oxygen species. Mol. Cell. Biol., 29(15):4080-4090.

[20]Takada, S., Inoue, E., Tano, K., Yoshii, H., Abe, T., Yoshimura, A., Akita, M., Tada, S., Watanabe, M., Seki, M., et al., 2009. Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2. Biochem. Biophys. Res. Commun., 379(2):233-238.

[21]Wang, Y., Liu, V.W., Xue, W.C., Cheung, A.N., Ngan, H.Y., 2006. Association of decreased mitochondrial DNA content with ovarian cancer progression. Br. J. Cancer, 95(8):1087-1091.

[22]Xu, Y., Fang, F., Dhar, S.K., Bosch, A., St. Clair, W.H., Kasarskis, E.J., St. Clair, D.K., 2008. Mutations in the SOD2 promoter reveal a molecular basis for an activating protein 2-dependent dysregulation of manganese superoxide dismutase expression in cancer cells. Mol. Cancer Res., 6(12):1881-1893.

[23]Ye, H., Wang, A., Lee, B.S., Yu, T., Sheng, S., Peng, T., Hu, S., Crowe, D.L., Zhou, X., 2008. Proteomic based identification of manganese superoxide dismutase 2 (SOD2) as a metastasis marker for oral squamous cell carcinoma. Cancer Genomics Proteomics, 5(2):85-94.

[24]Yogev, O., Yogev, O., Singer, E., Shaulian, E., Goldberg, M., Fox, T.D., Pines, O., 2010. Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response. PLoS Biol., 8(3):e1000328.

[25]Zejnilovic, J., Akev, N., Yilmaz, H., Isbir, T., 2009. Association between manganese superoxide dismutase polymorphism and risk of lung cancer. Cancer Genet. Cytogenet., 189(1):1-4.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE