Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells

Jhen Jia Fan, Wen Hsien Hsu, Hao Hsiang Hung, Wei Jun Zhang, Yu Lin A Lee, Ku Chung Chen, Cheng Ying Chu, Tzu Ping Ko, Ming Ting Lee, Cheng Wei Lin, Chia Hsiung Cheng

Research output: Contribution to journalArticle

Abstract

Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro-assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431-III cell line compared with that in the parental A431 cell line (A431-P). In the present study, high protein levels of MnSOD and H 2 O 2 production were observed in A431-III cells; however, catalase protein levels were significantly lower in A431-III cells compared with those in the A431-P cell line. The knockdown of MnSOD increased H 2 O 2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase-1, -2 and -9, and the migratory and invasive abilities of the cells. Inducing a reduction in H 2 O 2 using diphenyleneiodonium (DPI) and N.acetyl-l-cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H 2 O 2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.

Original languageEnglish
Pages (from-to)1639-1650
Number of pages12
JournalInternational Journal of Oncology
Volume54
Issue number5
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

Superoxide Dismutase
Squamous Cell Carcinoma
Reactive Oxygen Species
Luteolin
Cell Line
Quercetin
Catalase
Neoplasms
Homeostasis
Messenger RNA
Matrix Metalloproteinase 1
Proteins
Matrix Metalloproteinase 2
Antineoplastic Agents
Small Interfering RNA
Cysteine
Carcinogenesis
Oxidative Stress
Apoptosis
Neoplasm Metastasis

Keywords

  • Hydrogen peroxide
  • Luteolin
  • Manganese superoxide dismutase
  • Metastasis
  • Quercetin
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells. / Fan, Jhen Jia; Hsu, Wen Hsien; Hung, Hao Hsiang; Zhang, Wei Jun; A Lee, Yu Lin; Chen, Ku Chung; Chu, Cheng Ying; Ko, Tzu Ping; Lee, Ming Ting; Lin, Cheng Wei; Cheng, Chia Hsiung.

In: International Journal of Oncology, Vol. 54, No. 5, 01.04.2019, p. 1639-1650.

Research output: Contribution to journalArticle

Fan, Jhen Jia ; Hsu, Wen Hsien ; Hung, Hao Hsiang ; Zhang, Wei Jun ; A Lee, Yu Lin ; Chen, Ku Chung ; Chu, Cheng Ying ; Ko, Tzu Ping ; Lee, Ming Ting ; Lin, Cheng Wei ; Cheng, Chia Hsiung. / Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells. In: International Journal of Oncology. 2019 ; Vol. 54, No. 5. pp. 1639-1650.
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abstract = "Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro-assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431-III cell line compared with that in the parental A431 cell line (A431-P). In the present study, high protein levels of MnSOD and H 2 O 2 production were observed in A431-III cells; however, catalase protein levels were significantly lower in A431-III cells compared with those in the A431-P cell line. The knockdown of MnSOD increased H 2 O 2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase-1, -2 and -9, and the migratory and invasive abilities of the cells. Inducing a reduction in H 2 O 2 using diphenyleneiodonium (DPI) and N.acetyl-l-cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H 2 O 2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.",
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T1 - Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells

AU - Fan, Jhen Jia

AU - Hsu, Wen Hsien

AU - Hung, Hao Hsiang

AU - Zhang, Wei Jun

AU - A Lee, Yu Lin

AU - Chen, Ku Chung

AU - Chu, Cheng Ying

AU - Ko, Tzu Ping

AU - Lee, Ming Ting

AU - Lin, Cheng Wei

AU - Cheng, Chia Hsiung

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro-assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431-III cell line compared with that in the parental A431 cell line (A431-P). In the present study, high protein levels of MnSOD and H 2 O 2 production were observed in A431-III cells; however, catalase protein levels were significantly lower in A431-III cells compared with those in the A431-P cell line. The knockdown of MnSOD increased H 2 O 2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase-1, -2 and -9, and the migratory and invasive abilities of the cells. Inducing a reduction in H 2 O 2 using diphenyleneiodonium (DPI) and N.acetyl-l-cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H 2 O 2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.

AB - Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro-assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431-III cell line compared with that in the parental A431 cell line (A431-P). In the present study, high protein levels of MnSOD and H 2 O 2 production were observed in A431-III cells; however, catalase protein levels were significantly lower in A431-III cells compared with those in the A431-P cell line. The knockdown of MnSOD increased H 2 O 2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase-1, -2 and -9, and the migratory and invasive abilities of the cells. Inducing a reduction in H 2 O 2 using diphenyleneiodonium (DPI) and N.acetyl-l-cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H 2 O 2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.

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KW - Metastasis

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