Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro

Lima, Renilton Aires; Cândido, Eduardo Batista; Melo, Flávia Perrim de; Piedade, Josiane Barbosa; Vidigal, Paula Vieira Teixeira; Silva, Luciana Maria; Filho, Agnaldo Lopes da Silva

doi:10.1590/so100-720320150005292

Cited by 12 publications

(5 citation statements)

References 29 publications

(39 reference statements)

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“…In cancer cell lines, ibuprofen is also known to alter cell proliferation and viability, the resulting cell growth slowdown being often associated with cell cycle arrest. In many cases, such as colon carcinoma (Andrews et al, 2008;Janssen et al, 2006Janssen et al, , 2008, prostate cancer (Andrews et al, 2002(Andrews et al, , 2008Minnery and Getzenberg, 2005), oral cavity cancer cell lines (Kim et al, 2004;Thurnher et al, 2001) and ovarian cancer cell lines (Andrews et al, 2008;Duncan et al, 2012;Lima et al, 2015), ibuprofen also induces apoptosis. Similar to its mechanism of action in cancer cells, we observed that ibuprofen alters both proliferation and cell death in human fetal ovary.…”

Section: Ibuprofen Impacts the Growth Of The Human Fetal Ovarymentioning

confidence: 99%

“…Despite evidence implicating PGs and COXs as critical factors in adult female reproductive function (Duffy, 2015;Sugimoto et al, 2015), little is known about their precise function in human ovarian organogenesis. However, prostaglandin E2 (PGE2) signaling was related to enhanced expression of germ cell survival genes in human fetal ovaries (Bayne et al, 2009), and analgesics were found to induce cell death in human ovarian cancer cell lines (Andrews et al, 2008;Zerbini et al, 2011;Duncan et al, 2012;Lima et al, 2015). Therefore, we hypothesized that exposure of the developing ovary to COX inhibitors may have toxic effects on germ and/or somatic cells.…”

Section: Introductionmentioning

confidence: 99%

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Ibuprofen Is Deleterious for the Development of First-Trimester Human Fetal Ovary Ex Vivo

Leverrier-Penna

Mitchell

Becker

et al. 2018

Obstetrical &Amp; Gynecological Survey

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Does ibuprofen use during the first trimester of pregnancy interfere with the development of the human fetal ovary? SUMMARY ANSWER: In human fetuses, ibuprofen exposure is deleterious for ovarian germ cells. WHAT IS KNOWN ALREADY: In utero stages of ovarian development define the future reproductive capacity of a woman. In rodents, analgesics can impair the development of the fetal ovary leading to early onset of fertility failure. Ibuprofen, which is available over-thecounter, has been reported as a frequently consumed medication during pregnancy, especially during the first trimester when the ovarian germ cells undergo crucial steps of proliferation and differentiation. STUDY DESIGN, SIZE, DURATION: Organotypic cultures of human ovaries obtained from 7 to 12 developmental week (DW) fetuses were exposed to ibuprofen at 1-100 μM for 2, 4 or 7 days. For each individual, a control culture (vehicle) was included and compared to its treated counterpart. A total of 185 individual samples were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian explants were analyzed by flow cytometry, immunohistochemistry and quantitative PCR. Endpoints focused on ovarian cell number, cell death, proliferation and germ cell complement. To analyze the possible range of exposure, ibuprofen was measured in the umbilical cord blood from the women exposed or not to ibuprofen prior to termination of pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Human ovarian explants exposed to 10 and 100 μM ibuprofen showed reduced cell number, less proliferating cells, increased apoptosis and a dramatic loss of germ cell number, regardless of the gestational age of the fetus. Significant effects were observed after 7 days of exposure to 10 μM ibuprofen. At this concentration, apoptosis was observed as early as 2 days of treatment, along with a decrease in M2A-positive germ cell number. These deleterious effects of ibuprofen were not fully rescued after 5 days of drug withdrawal. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed in an experimental setting of human ovaries explants exposed to the drug in culture, which may not fully recapitulate the complexity of in vivo exposure and organ development. Inter-individual variability is also to be taken into account. WIDER IMPLICATIONS OF THE FINDINGS: Whereas ibuprofen is currently only contra-indicated after 24 weeks of pregnancy, our results points to a deleterious effect of this drug on first trimester fetal ovaries ex vivo. These findings deserve to be considered in light of the

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Section: Ibuprofen Impacts the Growth Of The Human Fetal Ovarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ibuprofen Is Deleterious for the Development of First-Trimester Human Fetal Ovary Ex Vivo

Leverrier-Penna

Mitchell

Becker

et al. 2018

Obstetrical &Amp; Gynecological Survey

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“…ABCD3 is involved in the transport of fatty acids in the peroxisome and may play an important role in tumorigenesis ( Reams et al., 2015 ). ABCD3 has been shown to be a biogenetic marker for malignancies such as human prostate cancer ( Zhang et al., 2020b ), ovarian cancer ( Lima et al., 2015 ; Elsnerova et al., 2016 ), and non-small cell lung cancer ( Tran, 2013 ) but has hardly been evaluated in glioma. Here, we screened ABCD3 as one of the most dramatically downregulated genes during oncolytic virus EV-A71 treatment.…”

Section: Discussionmentioning

confidence: 99%

ABCD3 is a prognostic biomarker for glioma and associated with immune infiltration: A study based on oncolysis of gliomas

Zhang

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundGliomas are the most lethal primary brain tumors and are still a major therapeutic challenge. Oncolytic virus therapy is a novel and effective means for glioma. However, little is known about gene expression changes during this process and their biological functions on glioma clinical characteristics and immunity.MethodsThe RNA-seq data after oncolytic virus EV-A71 infection on glioma cells were analyzed to screen significantly downregulated genes. Once ABCD3 was selected, The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) data were used to analyze the relationship between ABCD3 expression and clinical characteristics in glioma. We also evaluated the influence of ABCD3 on the survival of glioma patients. CIBERSORT and Tumor Immune Estimation Resource (TIMER) were also used to investigate the correlation between ABCD3 and cancer immune infiltrates. Gene set enrichment analysis (GSEA) was performed to functionally annotate the potential functions or signaling pathways related to ABCD3 expression.ResultsABCD3 was among the top 5 downregulated genes in glioma cells after oncolytic virus EV-A71 infection and was significantly enriched in several GO categories. Both the mRNA and protein expression levels of ABCD3 were upregulated in glioma samples and associated with the prognosis and grades of glioma patients. The Kaplan–Meier (K-M) curve analysis revealed that patients with high ABCD3 expression had shorter disease-specific survival (DSS) and overall survival (OS) than those with low ABCD3 expression. Moreover, ABCD3 expression could affect the immune infiltration levels and diverse immune marker sets in glioma. A positive correlation was found between ABCD3 and macrophages and active dendritic cells in the microenvironment of both the GBM and LGG. Gene sets including the plk1 pathway, tyrobp causal network, ir-damage and cellular response, and interleukin-10 signaling showed significant differential enrichment in the high ABCD3 expression phenotype.ConclusionOur results suggested that ABCD3 could be a potential biomarker for glioma prognosis and immunotherapy response and also further enriched the theoretical and molecular mechanisms of oncolytic virus treatment for malignant gliomas.

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“…Metamizole inhibited A549 lung cancer cell proliferation in a dose dependent manner while no induction of apoptotic cell death was detected (17). Clinical concentrations of acetaminophen inhibited cell growth in an epithelial ovarian tumor cell line in vitro (18). Vad et al reported a selective toxicity of acetaminophen towards melanoma cell lines, while no toxic effects were detected in other tumor entities such as colon and pancreas cancer cell lines (19).…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma Cell Lines In Vitro

Bundscherer

Malsy

Gruber

et al. 2018

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Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro

Abstract: This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally, TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 transporters.

Cited by 12 publications

References 29 publications

Ibuprofen Is Deleterious for the Development of First-Trimester Human Fetal Ovary Ex Vivo

Ibuprofen Is Deleterious for the Development of First-Trimester Human Fetal Ovary Ex Vivo

ABCD3 is a prognostic biomarker for glioma and associated with immune infiltration: A study based on oncolysis of gliomas

Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma Cell Lines In Vitro

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