Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma

Chae,Jung-Il; Cho,Jin  Hyoung; Lee,Kyung-Ae; Choi,Nag-Jin; Seo,Kang  Seok; Kim,Sang-Bum; Lee,Sang-Han; Shim,Jung-Hyun

doi:10.3892/ijmm.2012.1075

Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma

Authors:
- Jung-Il Chae
- Jin Hyoung Cho
- Kyung-Ae Lee
- Nag-Jin Choi
- Kang Seok Seo
- Sang-Bum Kim
- Sang-Han Lee
- Jung-Hyun Shim
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Affiliations: Department of Dental Pharmacology, School of Dentistry, Brain Korea 21 Project, Chonbuk National University, Jeonju 561-756, Republic of Korea, Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea, Department of Animal Science, College of Agricultural and Life Science, Chonbuk National University, Jeonju 561-756, Republic of Korea, Department of Animal Science and Technology, Sunchon National University, Suncheon 540-742, Republic of Korea, Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration (RDA), Suwon 441-706, Republic of Korea
Published online on: July 24, 2012 https://doi.org/10.3892/ijmm.2012.1075
Pages: 835-841

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Abstract

Quercetin (Qu) is found in plants, including red onions and in the skins of red apples, and induces the apoptosis of certain malignant cells. However, no report has been issued on the apoptotic effect of Qu on human malignant pleural mesothelioma. In the present study, it was found that MSTO‑211H mesothelioma cell viability was reduced and apoptotic cell death was increased by Qu (20-80 µM), which was found to have an IC50 of 58 µM. In addition, Qu increased the sub-G1 cell population, and was found to interact with specificity protein 1 (Sp1) and significantly suppressed its expression at the protein and mRNA levels. Furthermore, Qu modulated the levels of Sp1 regulatory genes, such as cyclin D1, myeloid cell leukemia (Mcl)-1 and survivin in MSTO-211H cells. Apoptotic signaling cascades were activated by the cleavage of Bid, caspase-3 and PARP, and by the downregulation of Bcl-xL and the upregulation of Bax in MSTO-211H cells. Our results strongly suggest that Sp1 be considered as a novel molecular target of Qu in human malignant pleural mesothelioma.

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1.	KH MieanS MohamedFlavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plantsJ Agric Food Chem4931063112200110.1021/jf000892m11410016
2.	GN KimHD JangProtective mechanism of quercetin and rutin using glutathione metabolism on HO-induced oxidative stress in HepG2 cellsAnn NY Acad Sci1171530537200910.1111/j.1749-6632.2009.04690.x19723100
3.	KV HirparaP AggarwalAJ MukherjeeN JoshiAC BurmanQuercetin and its derivatives: synthesis, pharmacological uses with special emphasis on anti-tumor properties and prodrug with enhanced bio-availabilityAnticancer Agents Med Chem9138161200910.2174/18715200978731385519199862
4.	L WangYC TuTW LianJT HungJH YenMJ WuDistinctive antioxidant and antiinflammatory effects of flavonolsJ Agric Food Chem5497989804200610.1021/jf062071917177504
5.	JN JakobsenJB SorensenReview on clinical trials of targeted treatments in malignant mesotheliomaCancer Chemother Pharmacol68115201110.1007/s00280-011-1655-321553148
6.	S ToyokuniMechanisms of asbestos-induced carcinogenesisNagoya J Med Sci711102009
7.	L LiJR DavieThe role of Sp1 and Sp3 in normal and cancer cell biologyAnn Anat192275283201010.1016/j.aanat.2010.07.01020810260
8.	LM KongCG LiaoF FeiX GuoJL XingZN ChenTranscription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancerCancer Sci10114631470201010.1111/j.1349-7006.2010.01554.x20384626
9.	UT SankpalS GoodisonM AbdelrahimR BashaTargeting Sp1 transcription factors in prostate cancer therapyMed Chem7518525201110.2174/15734061179679920322022994
10.	MC ArcherRole of sp transcription factors in the regulation of cancer cell metabolismGenes Cancer2712719201110.1177/194760191142302922207896
11.	J WanBA CarrNS CutlerDL LanzaRN HinesGS YostSp1 and Sp3 regulate basal transcription of the human CYP2F1 geneDrug Metab Dispos3312441253200510.1124/dmd.105.00406915860659
12.	X BaiH DengResearch progress on relationship between transcription factor Sp1 and tumorZhejiang Da Xue Xue Bao Yi Xue Ban392152202010(In Chinese)
13.	C CulverA MelvinS MudieS RochaHIF-1alpha depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugsCell Cycle1012491260201110.4161/cc.10.8.1532621412054
14.	L GibelliniM PintiM NasiQuercetin and cancer chemopreventionEvid Based Complement Alternat Med2011591356201121792362
15.	M LinsalataA OrlandoC MessaMG RefoloF RussoQuercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesisAnticancer Res3035013507201020944129
16.	M RussoC SpagnuoloS VolpeA MupoI TedescoGL RussoQuercetin induced apoptosis in association with death receptors and fludarabine in cells isolated from chronic lymphocytic leukaemia patientsBr J Cancer103642648201010.1038/sj.bjc.6605794
17.	T ThangasamyS SittadjodyGC MitchellQuercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73BMC Cancer10282201010.1186/1471-2407-10-28220540768
18.	J Gonzalez-GallegoMV Garcia-MediavillaS Sanchez-CamposMJ TunonFruit polyphenols, immunity and inflammationBr J Nutr104Suppl 3S15S27201010.1017/S000711451000391020955647
19.	JH ShimHS ChoiA Pugliese(-)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinaseJ Biol Chem2832837028379200810.1074/jbc.M80220020018687687
20.	TA ZykovaF ZhuX ZhaiResveratrol directly targets COX-2 to inhibit carcinogenesisMol Carcinog47797805200810.1002/mc.2043718381589
21.	ES ChoiJH ShimJY JungApoptotic effect of tolfenamic acid in androgen receptor-independent prostate cancer cell and xenograft tumor through specificity protein 1Cancer Sci102742748201110.1111/j.1349-7006.2011.01871.x21241418
22.	JH ShimJA ShinJY JungChemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1Eur J Cancer Prev20102111201110.1097/CEJ.0b013e328341e38f21131823
23.	A VachaniE MoonE WakeamSM AlbeldaGene therapy for mesothelioma and lung cancerAm J Respir Cell Mol Biol42385393201010.1165/rcmb.2010-0026RT20160042
24.	A VachaniE MoonE WakeamAR HaasDH StermanSM AlbeldaGene therapy for lung neoplasmsClin Chest Med32865885201110.1016/j.ccm.2011.08.006
25.	ES ChoiSD ChoJG JeonNP ChoThe apoptotic effect of the hexane extract of Rheum undulatum L. in oral cancer cells through the down-regulation of specificity protein 1 and survivinLab Anim Res271924201121826155
26.	E ChiefariA BrunettiF ArturiIncreased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?BMC Cancer235200210.1186/1471-2407-2-3512475396
27.	Y HosoiT WatanabeK NakagawaUp-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancerInt J Oncol25461468200415254745
28.	L WangD WeiS HuangTranscription factor Sp1 expression is a significant predictor of survival in human gastric cancerClin Cancer Res963716380200314695137
29.	JC YaoL WangD WeiAssociation between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancerClin Cancer Res1041094117200410.1158/1078-0432.CCR-03-0628
30.	A ZannettiS Del VecchioMV CarrieroCoordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinomaCancer Res6015461551200010749121
31.	Y ShuklaJ GeorgeCombinatorial strategies employing nutraceuticals for cancer developmentAnn NY Acad Sci1229162175201110.1111/j.1749-6632.2011.06104.x21793852
32.	LL ZaminEC Filippi-ChielaP Dillenburg-PillaF HornC SalbegoG LenzResveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cellsCancer Sci10016551662200910.1111/j.1349-7006.2009.01215.x19496785
33.	A MurakamiH AshidaJ TeraoMultitargeted cancer prevention by quercetinCancer Lett269315325200810.1016/j.canlet.2008.03.046
34.	FO RanellettiN MaggianoFG SerraQuercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumorsInt J Cancer85438445200010.1002/(SICI)1097-0215(20000201)85:3%3C438::AID-IJC22%3E3.0.CO;2-F10652438
35.	MJ van ErkP RoepmanTR van der LendeIntegrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitroEur J Nutr44143156200515309432
36.	WH WatsonJ CaiDP JonesDiet and apoptosisAnnu Rev Nutr20485505200010.1146/annurev.nutr.20.1.485
37.	SC ShenYC ChenFL HsuWR LeeDifferential apoptosis-inducing effect of quercetin and its glycosides in human promyeloleukemic HL-60 cells by alternative activation of the caspase 3 cascadeJ Cell Biochem8910441055200310.1002/jcb.1055912874837
38.	RL SinghalYA YehN PrajaE OlahGW Sledge JrG WeberQuercetin down-regulates signal transduction in human breast carcinoma cellsBiochem Biophys Res Commun208425431199510.1006/bbrc.1995.13557887960
39.	YS ChiHG JongKH SonHW ChangSS KangHP KimEffects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: cyclooxygenases and lipoxygenasesBiochem Pharmacol6211851191200110.1016/S0006-2952(01)00773-011705451
40.	CS OngE TranTT NguyenQuercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressionsOncol Rep117277332004
41.	SW BlumeRC SnyderR RayS ThomasCA KollerDM MillerMithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivoJ Clin Invest8816131621199110.1172/JCI1154741834700
42.	S ChintharlapalliS PapineniP LeiS PathiS SafeBetulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factorsBMC Cancer11371201110.1186/1471-2407-11-371
43.	M PietrzakM Puzianowska-Kuznickap53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoterBiol Chem389383393200810.1515/BC.2008.03918208354