Isobaric tags for relative and absolute quantitation‑based proteomics analysis of the effect of ginger oil on bisphenol A‑induced breast cancer cell proliferation

Lei,Dan; Hong,Tao; Li,Longxue; Chen,Lai; Luo,Xiaoquan; Wu,Qinghua; Liu,Zhiyong

doi:10.3892/ol.2020.12362

Isobaric tags for relative and absolute quantitation‑based proteomics analysis of the effect of ginger oil on bisphenol A‑induced breast cancer cell proliferation

Authors:
- Dan Lei
- Tao Hong
- Longxue Li
- Lai Chen
- Xiaoquan Luo
- Qinghua Wu
- Zhiyong Liu
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Affiliations: Experimental Animal Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China, School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China, Basic Medical College, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China
Published online on: December 8, 2020 https://doi.org/10.3892/ol.2020.12362
Article Number: 101
Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Several chemicals in the environment, particularly those with estrogenic activity and small amounts (micromolar or lower) of environmental estrogen can cause changes in cell function and interfere with endocrine functions of animals and humans. These compounds enter the human body and increase the load of estrogen in the body, leading to an increasing incidence of estrogen‑related tumors in breast cancer, ovarian cancer and endometrial cancer. Previous studies have demonstrated that ginger can inhibit the expression of estrogen receptors, while the bioactive ingredients of ginger sig‑nificantly inhibit proliferation and promote the apoptosis of breast cancer cells. In the present study, a quantitative proteomics technique based on relative and absolute quanti‑tative isobaric labeling was used to determine the effect of ginger essential oil (GEO) and BPA combined treatment on the proteomic characteristics of MCF‑7 cells. In total, 5,084 proteins were detected. Proteins that were upregulated >1.2‑fold and downregu‑lated by >0.8‑fold were differentially expressed. Overall, 528 differentially expressed proteins were identified. Compared with the control group, MCF‑7 cells treated with GEO, BPA and GEO‑BPA resulted in 45 (14 up‑ and 31 downregulated), 481 (141 up‑ and 340 downregulated) and 34 (13 up‑ and 21 downregulated) differentially ex‑pressed proteins, respectively. Compared with the BPA group, MCF- 7 cells treated with GEO-BPA resulted in 210 (117 up- and 93 downregulated ) differentially expressed proteins, among the 210 differentially expressed proteins in the GEO-BPA group, 10 proteins were associated with oxidative phosphorylation pathways, while succinate dehydrogenase (ubiquinone) iron‑sulfur subunit (SDHB), succinate dehydrogenase cytochrome b560 subunit, mitochondrial (SDHC), cytochrome c oxidase subunit 2 and superoxide dismutase (Mn), mitochondrial (SOD2) expression was decreased with GEO‑BPA combined treatment. Through the analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, the cellular localization, func‑tional annotation and biological pathways of differentially expressed proteins were ex‑amined. The results indicated that GEO‑BPA may act through the oxidative phosphory‑lation pathway, decreased the expression of SDHB and SDHC, affected the tricarbox‑ylic acid cycle and decreased the expression of SOD2. This may have led to oxidative stress and the death of breast cancer cells, and the SDH signaling pathway may be an important mediator of the inhibitory effects of GEO in MCF‑7 breast cancer cells. GEO can inhibit the proliferation of breast cancer MCF‑7 cells induced by BPA, and the underlying mechanism may be associated with oxidative phosphorylation. These results may aid the development of future treatment strategies for breast cancer caused by environmental estrogen exposure.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Derouiche S, Warnier M, Mariot P, Gosset P, Mauroy B, Bonnal JL, Slomianny C, Delcourt P, Prevarskaya N and Roudbaraki M: Bisphenol A stimulates human prostate cancer cell migration via remodelling of calcium signalling. Springerplus. 2:542013. View Article : Google Scholar : PubMed/NCBI
3	Kloukos D, Pandis N and Eliades T: In vivo bisphenol - a release from dental pit and fissure sealants: A systematic review. J Dent. 41:659–667. 2013. View Article : Google Scholar : PubMed/NCBI
4	Krishnan AV, Stathis P, Permuth SF, Tokes L and Feldman D: Bisphenol-A: An estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology. 132:2279–2286. 1993. View Article : Google Scholar : PubMed/NCBI
5	Huang YQ, Wong CK, Zheng JS, Bouwman H, Barra R, Wahlström B, Neretin L and Wong MH: Bisphenol A (BPA) in China: A review of sources, environmental levels, and potential human health impacts. Environ Int. 42:91–99. 2012. View Article : Google Scholar : PubMed/NCBI
6	Rogers JA, Metz L and Yong VW: Review: Endocrine disrupting chemicals and immune responses: a focus on bisphenol-A and its potential mechanisms. Mol Immunol. 53:421–430. 2013. View Article : Google Scholar : PubMed/NCBI
7	Vom Saal FS, Nagel SC, Coe BL, Angle BM and Taylor JA: The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Mol Cell Endocrinol. 354:74–84. 2012. View Article : Google Scholar : PubMed/NCBI
8	Lui YZ, Zeng GQ, Ge LC, Liu H, Du J and Wang HS: Bisphenol A induces epithelial mesenchymalization of human breast cancer MCF-7 cells. Acta Scientiae Circumstantiae. 35:608–612. 2015.(In Chinese).
9	White B: Ginger: An overview. Am Fam Physician. 75:1689–1691. 2007.PubMed/NCBI
10	Ali BH, Blunden G, Tanira MO and Nemmar A: Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food Chem Toxicol. 46:409–420. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K and Goto H: Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun. 362:218–223. 2007. View Article : Google Scholar : PubMed/NCBI
12	Jeong C-H, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, Jeon YJ, Li H, Jiang H and Dong Z: [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res. 69:5584–5591. 2009. View Article : Google Scholar : PubMed/NCBI
13	Surh YJ, Park KK, Chun KS, Lee LJ, Lee E and Lee SS: Anti-tumor-promoting activities of selected pungent phenolic substances present in ginger. J Environ Pathol Toxicol Oncol. 18:131–139. 1999.PubMed/NCBI
14	Brahmbhatt M, Gundala SR, Asif G, Shamsi SA and Aneja R: Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation. Nutr Cancer. 65:263–272. 2013. View Article : Google Scholar : PubMed/NCBI
15	Santos PA SR, Avanço GB, Nerilo SB, Marcelino RIA, V. Janeiro V, Valadares MC and Machinski M: Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalis L.), Turmeric (Curcuma longa L.), and Ginger (Zingiber officinale R.) Essential Oils in Cervical Cancer Cells (HeLa). ScientificWorldJournal. 2016:92730782016. View Article : Google Scholar : PubMed/NCBI
16	Prasad S and Tyagi AK: Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Pract. 2015:1429792015. View Article : Google Scholar : PubMed/NCBI
17	Karki N: Inhibitory activity of ginger oil against breast cancer cells (2011). LSU Master's Theses. 1714. simplehttps://digitalcommons.lsu.edu/gradschool_theses/1714
18	Brooks SC, Locke ER and Soule HD: Estrogen receptor in a human cell line (MCF-7) from breast carcinoma. J Biol Chem. 248:6251–6253. 1973.PubMed/NCBI
19	Ninth Chinese Pharmacopoeia Commission: Pharmacopoeia of the People's Republic of China (1). China Medical Science and Technology Press; China: pp. 932010
20	Kan Y, Lyu Q, Jiang N, Han S, Li J, Burdman S and Luo L: iTRAQ-based proteomic analyses of the plant-pathogenic bacterium Acidovorax citrulli during entrance into and resuscitation from the viable but nonculturable state. J Proteomics. 211:1035472020. View Article : Google Scholar : PubMed/NCBI
21	Gao Z, Wang J, Bai Y, Bao J and Dal E: Identification and Verification of the Main Differentially Expressed Proteins in Gastric Cancer via iTRAQ Combined with Liquid Chromatography-Mass Spectrometry. Anal Cell Pathol. 2019:53106842019. View Article : Google Scholar
22	Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al: STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47D:D607–D613. 2019. View Article : Google Scholar
23	Swaney DL, Wenger CD and Coon JJ: Value of using multiple proteases for large-scale mass spectrometry-based proteomics. J Proteome Res. 9:1323–1329. 2010. View Article : Google Scholar : PubMed/NCBI
24	Kanehisa M and Goto S: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar : PubMed/NCBI
25	Yu LR, Zeng R, Shao XX, Wang N, Xu YH and Xia QC: Identification of differentially expressed proteins between human hepatoma and normal liver cell lines by two-dimensional electrophoresis and liquid chromatography-ion trap mass spectrometry. Electrophoresis. 21:3058–3068. 2000. View Article : Google Scholar : PubMed/NCBI
26	Unwin RD, Griffiths JR and Whetton AD: Simultaneous analysis of relative protein expression levels across multiple samples using iTRAQ isobaric tags with 2D nano LC-MS/MS. Nat Protoc. 5:1574–1582. 2010. View Article : Google Scholar : PubMed/NCBI
27	Jamaluddin MFB, Nagendra PB, Nahar P, Oldmeadow C and Tanwar PS: Proteomic Analysis Identifies Tenascin-C Expression Is Upregulated in Uterine Fibroids. Reprod Sci. 26:476–486. 2019. View Article : Google Scholar : PubMed/NCBI
28	Feifei S and Yinyin W: Research status and progress of relationship between environmental bisphenol A and reproductive system malignant tumors. Health Res. 38:532–537. 2018.
29	Lui Q, Hu LG, Zhou QF and Jiang GB: Tetrabromobisphenol A bis(2-hydroxyethylether) induced dysfunction of respiratory chain oxidative phosphorylation and energy metabolism rat pheochromocytoma cells by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Chinese J Chromatography. 35:1–7. 2017. View Article : Google Scholar
30	Li QX, Zhang P and Liu H: Characteristics and progress of energy metabolism of tumor cells. Chinese Pharmacological Bulletin. 33:1499–1502. 2017.
31	Liberti MV and Locasale JW: The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 41:2872016. View Article : Google Scholar : PubMed/NCBI
32	Jose C, Bellance N and Rossignol R: Choosing between glycolysis and oxidative phosphorylation: A tumor's dilemma? Biochim Biophys Acta. 1807:552–561. 2011. View Article : Google Scholar : PubMed/NCBI
33	Sharma P and Singh S: Combinatorial Effect of DCA and Let-7a on Triple-Negative MDA-MB-231 Cells: A Metabolic Approach of Treatment. Integr Cancer Ther. 19:15347354209114372020. View Article : Google Scholar : PubMed/NCBI
34	Fan XX, Su N, Huang XJ, Li YF, Jia A, Fan JP, Wang AF, Zhao NM and Ma YC: Jar-TTA, a natural diterpenoid derivatives, induces apoptosis in human esophageal cancer cells through dual inhibition of glycolysis and oxidative phosphorylation. Chinese Pharmacological Bulletin. 35:950–957. 2019.
35	Guzy RD, Sharma B, Bell E, Chandel NS and Schumacker PT: Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol. 28:718–731. 2008. View Article : Google Scholar : PubMed/NCBI
36	Goffrini P, Ercolino T, Panizza E, Giachè V, Cavone L, Chiarugi A, Dima V, Ferrero I and Mannelli M: Functional study in a yeast model of a novel succinate dehydrogenase subunit B gene germline missense mutation (C191Y) diagnosed in a patient af-fected by a glomus tumor. Hum Mol Genet. 18:1860–1868. 2009. View Article : Google Scholar : PubMed/NCBI
37	Guzy RD, Sharma B, Bell E, Chandel NS and Schumacker PT: Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol. 28:718–731. 2008. View Article : Google Scholar : PubMed/NCBI
38	Slane BG, Aykin-Burns N, Smith BJ, Kalen AL, Goswami PC, Domann FE and Spitz DR: Mutation of succinate dehydrogenase subunit C results in increased O₂.-, oxidative stress, and genomic instability. Cancer Res. 66:7615–7620. 2006. View Article : Google Scholar : PubMed/NCBI
39	Zelko IN, Mariani TJ and Folz RJ: Superoxide dismutase multigene family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 33:337–349. 2002. View Article : Google Scholar : PubMed/NCBI
40	Han H, Yang S, Lin SG, Xu CS and Han ZH: Effects and mechanism of downregulation of COX 2 expression by RNA interference on proliferation and apoptosis of hu-man breast cancer MCF 7 cells. Mol Med Rep. 10:3092–3098. 2014. View Article : Google Scholar : PubMed/NCBI
41	Gomez-Lazaro M, Galindo MF, Melero-Fernandez de Mera RM, Fernandez-Gómez FJ, Concannon CG, Segura MF, Comella JX, Prehn JH and Jordan J: Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mito-chondrial cytochrome c release and apoptosis in response to malonate. Mol Pharmacol. 71:736–743. 2007. View Article : Google Scholar : PubMed/NCBI
42	Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N and Bossy-Wetzel E: Com plex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ. 16:899–909. 2009. View Article : Google Scholar : PubMed/NCBI
43	Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO and Enríquez JA: NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab. 16:378–386. 2012. View Article : Google Scholar : PubMed/NCBI