Dimethyl Sulfoxide Promotes the Multiple Functions of the Tumor Suppressor HLJ1 through Activator Protein-1 Activation in NSCLC Cells
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{"title"=>"Dimethyl sulfoxide promotes the multiple functions of the tumor suppressor HLJ1 through activator protein-1 activation in NSCLC cells", "type"=>"journal", "authors"=>[{"first_name"=>"Chi Chung", "last_name"=>"Wang", "scopus_author_id"=>"57154866400"}, {"first_name"=>"Sheng Yi", "last_name"=>"Lin", "scopus_author_id"=>"36630552400"}, {"first_name"=>"Yi Hua", "last_name"=>"Lai", "scopus_author_id"=>"55189411500"}, {"first_name"=>"Ya Jung", "last_name"=>"Liu", "scopus_author_id"=>"36450949500"}, {"first_name"=>"Yuan Lin", "last_name"=>"Hsu", "scopus_author_id"=>"55190075200"}, {"first_name"=>"Jeremy J W", "last_name"=>"Chen", "scopus_author_id"=>"7501892959"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22529897", "issn"=>"19326203", "sgr"=>"84859807190", "pui"=>"364638465", "scopus"=>"2-s2.0-84859807190", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0033772"}, "id"=>"17334c0a-d9e9-3e9d-a8c6-727e3b153201", "abstract"=>"BACKGROUND: Dimethyl sulfoxide (DMSO) is an amphipathic molecule that displays a diversity of antitumor activities. Previous studies have demonstrated that DMSO can modulate AP-1 activity and lead to cell cycle arrest at the G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is regulated by the transcription factor AP-1. However, the effects of DMSO on HLJ1 are still unknown. In the present study, we investigate the antitumor effects of DMSO through HLJ1 induction and demonstrate the mechanisms involved.\\n\\nMETHODS AND FINDINGS: Low-HLJ1-expressing highly invasive CL1-5 lung adenocarcinoma cells were treated with various concentrations of DMSO. We found that DMSO can significantly inhibit cancer cell invasion, migration, proliferation, and colony formation capabilities through upregulation of HLJ1 in a concentration-dependent manner, whereas ethanol has no effect. In addition, the HLJ1 promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates HLJ1 expression through an AP-1 site within the HLJ1 enhancer. The AP-1 subfamily members JunD and JunB were significantly upregulated by DMSO in a concentration-dependent manner. Furthermore, pretreatment with DMSO led to a significant increase in the percentage of UV-induced apoptotic cells.\\n\\nCONCLUSIONS: Our results suggest that DMSO may be an important stimulator of the tumor suppressor protein HLJ1 through AP-1 activation in highly invasive lung adenocarcinoma cells. Targeted induction of HLJ1 represents a promising approach for cancer therapy, which also implied that DMSO may serve as a potential lead compound or coordinated ligand for the development of novel anticancer drugs.", "link"=>"http://www.mendeley.com/research/dimethyl-sulfoxide-promotes-multiple-functions-tumor-suppressor-hlj1-through-activator-protein1-acti", "reader_count"=>34, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>7, "Student > Bachelor"=>9}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>7, "Student > Bachelor"=>9}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>4, "Neuroscience"=>1, "Chemistry"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Finland"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/335026", "https://ndownloader.figshare.com/files/335084"], "description"=>"<div><h3>Background</h3><p>Dimethyl sulfoxide (DMSO) is an amphipathic molecule that displays a diversity of antitumor activities. Previous studies have demonstrated that DMSO can modulate AP-1 activity and lead to cell cycle arrest at the G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is regulated by the transcription factor AP-1. However, the effects of DMSO on HLJ1 are still unknown. In the present study, we investigate the antitumor effects of DMSO through HLJ1 induction and demonstrate the mechanisms involved.</p> <h3>Methods and Findings</h3><p>Low-HLJ1-expressing highly invasive CL1–5 lung adenocarcinoma cells were treated with various concentrations of DMSO. We found that DMSO can significantly inhibit cancer cell invasion, migration, proliferation, and colony formation capabilities through upregulation of HLJ1 in a concentration-dependent manner, whereas ethanol has no effect. In addition, the <em>HLJ1</em> promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates <em>HLJ1</em> expression through an AP-1 site within the <em>HLJ1</em> enhancer. The AP-1 subfamily members JunD and JunB were significantly upregulated by DMSO in a concentration-dependent manner. Furthermore, pretreatment with DMSO led to a significant increase in the percentage of UV-induced apoptotic cells.</p> <h3>Conclusions</h3><p>Our results suggest that DMSO may be an important stimulator of the tumor suppressor protein HLJ1 through AP-1 activation in highly invasive lung adenocarcinoma cells. Targeted induction of HLJ1 represents a promising approach for cancer therapy, which also implied that DMSO may serve as a potential lead compound or coordinated ligand for the development of novel anticancer drugs.</p> </div>", "links"=>[], "tags"=>["dimethyl", "sulfoxide", "promotes", "functions", "suppressor", "hlj1", "activator", "protein-1", "activation", "nsclc", "cells"], "article_id"=>126186, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.s001", "https://dx.doi.org/10.1371/journal.pone.0033772.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dimethyl_Sulfoxide_Promotes_the_Multiple_Functions_of_the_Tumor_Suppressor_HLJ1_through_Activator_Protein_1_Activation_in_NSCLC_Cells/126186", "title"=>"Dimethyl Sulfoxide Promotes the Multiple Functions of the Tumor Suppressor HLJ1 through Activator Protein-1 Activation in NSCLC Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-17 01:43:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/652114"], "description"=>"<p>(A) The viability of lung adenocarcinoma CL1–5 cells cultured with various concentrations of DMSO by MTT assay. *<i>P</i> < 0.0005, #<i>P</i> < 0.0001 significantly different from the vehicle-treated control. (B) CL1–5 cells treated with or without DMSO were stained with phalloidin-tetramethylrhodamine isothiocyanate conjugate to detect F-actin (red). DMSO-treated cells exhibit fewer filopodia fibers, whereas the high concentration of DMSO (5%) leads to the cell death. The cell nuclei were counter stained with DAPI. The image magnification is×400.</p>", "links"=>[], "tags"=>["concentrations", "dmso"], "article_id"=>322604, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_various_concentrations_of_DMSO_on_CL1_8211_5_cell_viability_/322604", "title"=>"Effects of various concentrations of DMSO on CL1–5 cell viability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:43:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/652238"], "description"=>"<p>(A) Real-time quantitative RT-PCR reveals that HLJ1 mRNA expression was induced by DMSO in a concentration-dependent manner (0.1–2%, v/v) after 48 h incubation. (B) Concentration-dependent DMSO-induced HLJ1 expression at the protein level was confirmed by Western blot analysis. α-tubulin was a control for protein loading and transfer. (C) Time-dependent DMSO-induced HLJ1 expression at the mRNA level was verified by real-time quantitative RT-PCR. The results indicated that the mRNA level of HLJ1 was significantly increased after 2% DMSO treatment for 2 h. *<i>P</i> < 0.05, significantly different from the vehicle-treated control. (D) The protein expression level of HLJ1 after 2% DMSO treatment at the indicated time was detected by Western blot analysis. The result indicated that HLJ1 protein expression was time-dependent and was sustained with DMSO treatment for 48 h. α-tubulin was a control for protein loading and transfer.</p>", "links"=>[], "tags"=>["induces", "hlj1", "concentration-dependent", "time-dependent"], "article_id"=>322725, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DMSO_induces_HLJ1_expression_in_concentration_dependent_and_time_dependent_manners_/322725", "title"=>"DMSO induces HLJ1 expression in concentration-dependent and time-dependent manners.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:45:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/652351"], "description"=>"<p>(A) Relative luciferase activities of pGL3-FRER’ (containing the full-length HLJ1 promoter and enhancer) were determined in CL1–5 cells treated with various concentrations of DMSO. The results were correlated with the luciferase activity from cotransfected pSV-β-Gal cells and expressed as relative luciferase activity. *<i>P</i> < 0.05, significantly different from the vehicle-treated control. (B) 5′ deletion constructs of the HLJ1 promoter were represented in the upper panel. Relative luciferase activities of pGL3-F1RER’ and pGL3-F2RER’ (containing the full-length HLJ1 promoter with or without the AP-1 site, respectively) were determined in CL1–5 cells treated with or without 2% DMSO. (C) The mutation analysis of the AP-1 site within the <i>HLJ1</i> minimum enhancer indicated that the AP-1 site is critical for DMSO-induced <i>HLJ1</i> promoter activity. *<i>P</i> < 0.05, wild-type AP-1 site constructs compared with mutants. These results are representative of three independent experiments. (D) Further AP-1 site mutation analysis of the <i>HLJ1</i> minimum enhancer was confirmed by luciferase assay. The mutant derivative of the enhancer region where the motif was substituted was fused to the pGL3-promoter vector. Emi-F/APR1, the constructs of site-directed mutagenesis of the AP-1 site; Emi-SPF/R, the constructs of site-directed mutagenesis of the SP1 site. The results were correlated with the luciferase activity from cotransfected pSV-β-Gal cells and expressed as relative luciferase activity. *<i>P</i> < 0.05, compared with pGL3-promoter control. DMSO increases <i>HLJ1</i> enhancer activity through the AP-1 site in a concentration-dependent manner.</p>", "links"=>[], "tags"=>["transcriptional"], "article_id"=>322843, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Up_regulation_of_HLJ1_transcriptional_activity_by_DMSO_/322843", "title"=>"Up-regulation of <i>HLJ1</i> transcriptional activity by DMSO.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:47:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/652475"], "description"=>"<p>(A) Western blotting analysis shows that the expressions of the components of AP-1 (JunD and JunB) are regulated by DMSO in a dose-dependent manner, whereas the expression of Fra-1 shows no change with DMSO treatment. (B) CL1–5 cells transfected with JunD siRNA or the scrambled siRNA control were treated with or without 2% DMSO for 24 h and then analyzed by Western blotting. Knock-down of JunD decreased DMSO-induced HLJ1 expression. Data are representative of at least two independent experiments with β-actin used as the internal control.</p>", "links"=>[], "tags"=>["induces", "hlj1"], "article_id"=>322965, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DMSO_induces_HLJ1_expression_through_AP_1_/322965", "title"=>"DMSO induces HLJ1 expression through AP-1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:49:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/652629"], "description"=>"<p>(A) DMSO decreases cancer cell migration ability, as assessed by a scratch wound healing assay. The track was photographed immediately and after various times as indicated after wounding. The number of cells that migrated into the cell-free zone was evaluated (B). The results are expressed as the total number of the migrated cells. These results are representative of two independent experiments performed in triplicate. *<i>P</i> < 0.05, significantly different from the vehicle-treated control at the indicated time. (C) Invasiveness of CL1–5 cells treated with or without DMSO was evaluated by the Matrigel-based transwell invasion assay. Columns, mean derived from three separate experiments done in triplicate; bars, SD. *<i>P</i> < 0.05, significantly different from the vehicle-treated control.</p>", "links"=>[], "tags"=>["capabilities", "cells", "dmso"], "article_id"=>323116, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Suppression_of_in_vitro_migration_and_invasion_capabilities_of_CL1_5_cells_by_DMSO_treatment_/323116", "title"=>"Suppression of <i>in vitro</i> migration and invasion capabilities of CL1–5 cells by DMSO treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:51:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/652726"], "description"=>"<p>(A) The proliferation of CL1–5 cells treated with various concentrations of DMSO was assessed by MTT assay (n  =  6 per group). #<i>P</i> < 0.05, 0.1–1% DMSO treatment significantly different from the no-treated control. *<i>P</i> < 0.05, 2% DMSO treatment significantly different from the no-treated control. (B) DMSO inhibits the anchorage-dependent colony formation of CL1–5 cells (n  =  4 per group). *<i>P</i> < 0.05, significantly different from the no-treated control. (C) Anchorage-independent colony formation of CL1–5 cells was determined by soft agar assay (n  =  4 per group). DMSO inhibits the anchorage-independent colony formation of CL1–5 cells. *<i>P</i> < 0.05, significantly different from the no-treated control.</p>", "links"=>[], "tags"=>["proliferation", "cells", "dmso"], "article_id"=>323221, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_proliferation_and_colony_formation_of_CL1_8211_5_cells_by_DMSO_treatment_/323221", "title"=>"Inhibition of proliferation and colony formation of CL1–5 cells by DMSO treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:53:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/652823"], "description"=>"<p>(A) DMSO enhances PARP cleavage caused by UV-irradiation. After DMSO and UV treatments, CL1–5 cells were analyzed by Western blotting with anti-PARP and HLJ1 antibodies. GAPDH was used as an internal control. (B) Quantitative results of three independent western blotting analyses are shown. *<i>P</i> < 0.05, #<i>P</i>  =  0.014, compared with DMSO untreated control. (C) DMSO increases UV-induced apoptosis. CL1–5 cells were pretreated with DMSO and exposed to UV-irradiation. After a 48 h recovery period, the percentages of apoptotic cells were quantified by flow cytometry and presented as the means ± S.D. of three experiments. *<i>P</i> < 0.05, #<i>P</i> < 0.01, significantly different from the cells pretreated without DMSO and exposed to UV irradiation.</p>", "links"=>[], "tags"=>["dmso", "uv-induced"], "article_id"=>323309, "categories"=>["Cancer", "Biochemistry", "Chemistry", "Genetics"], "users"=>["Chi-Chung Wang", "Sheng-Yi Lin", "Yi-Hua Lai", "Ya-Jung Liu", "Yuan-Lin Hsu", "Jeremy J. W. Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033772.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_DMSO_treatment_on_UV_induced_apoptosis_/323309", "title"=>"Effect of DMSO treatment on UV-induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-17 00:55:09"}

PMC Usage Stats | Further Information

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Relative Metric

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