Cytotoxic, apoptotic and cell migration inhibitory effects of atranorin on SPC212 mesothelioma cells
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摘要
Objective: To investigate the effects of atranorin, a lichen secondary metabolite, on SPC212 malignant mesothelioma cells in vitro. Methods: SPC212 malignant mesothelioma cell line was used. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxic effects of atranorin and cisplatin at 24, 48 and 72 h. Hematoxylin-eosin staining and 4',6-diamidino-2-phenylindole, dihydrochloride staining were used for determining cell and nucleus morphology, respectively. Wound healing assay was used for investigating cell migration. The xCELLigence real-time cell analysis system was used for determining cell proliferation.Results: Atranorin at 5-450 μM decreased cell viability at 24, 48 and 72 h. IC_(50) values of atranorin were 300.94, 292.6 and 278.02 μM at 24, 48 and 72 h, respectively; meanwhile, the IC50 values of cisplatin were 128.00, 34.37 and 17.05 μM at 24, 48 and 72 h, respectively. Furthermore, atranorin disrupted cell and nuclear morphology with increasing concentrations. Atranorin significantly reduced cell migration by 38%, 37% and 35% at 300, 250 and 200 μM, respectively(P<0.000). Atranorin at 160-450 μM decreased cell proliferation at 72 h(P<0.000).Conclusions: Atranorin has cytotoxic, antiproliferative, apoptotic and cell migration inhibitory effects on SPC212 malignant mesothelioma cancer cells.
Objective: To investigate the effects of atranorin, a lichen secondary metabolite, on SPC212 malignant mesothelioma cells in vitro. Methods: SPC212 malignant mesothelioma cell line was used. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxic effects of atranorin and cisplatin at 24, 48 and 72 h. Hematoxylin-eosin staining and 4',6-diamidino-2-phenylindole, dihydrochloride staining were used for determining cell and nucleus morphology, respectively. Wound healing assay was used for investigating cell migration. The xCELLigence real-time cell analysis system was used for determining cell proliferation.Results: Atranorin at 5-450 μM decreased cell viability at 24, 48 and 72 h. IC50 values of atranorin were 300.94, 292.6 and 278.02 μM at 24, 48 and 72 h, respectively; meanwhile, the IC_(50) values of cisplatin were 128.00, 34.37 and 17.05 μM at 24, 48 and 72 h, respectively. Furthermore, atranorin disrupted cell and nuclear morphology with increasing concentrations. Atranorin significantly reduced cell migration by 38%, 37% and 35% at 300, 250 and 200 μM, respectively(P<0.000). Atranorin at 160-450 μM decreased cell proliferation at 72 h(P<0.000).Conclusions: Atranorin has cytotoxic, antiproliferative, apoptotic and cell migration inhibitory effects on SPC212 malignant mesothelioma cancer cells.
Objective: To investigate the effects of atranorin, a lichen secondary metabolite, on SPC212 malignant mesothelioma cells in vitro. Methods: SPC212 malignant mesothelioma cell line was used. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxic effects of atranorin and cisplatin at 24, 48 and 72 h. Hematoxylin-eosin staining and 4',6-diamidino-2-phenylindole, dihydrochloride staining were used for determining cell and nucleus morphology, respectively. Wound healing assay was used for investigating cell migration. The xCELLigence real-time cell analysis system was used for determining cell proliferation.Results: Atranorin at 5-450 μM decreased cell viability at 24, 48 and 72 h. IC50 values of atranorin were 300.94, 292.6 and 278.02 μM at 24, 48 and 72 h, respectively; meanwhile, the IC_(50) values of cisplatin were 128.00, 34.37 and 17.05 μM at 24, 48 and 72 h, respectively. Furthermore, atranorin disrupted cell and nuclear morphology with increasing concentrations. Atranorin significantly reduced cell migration by 38%, 37% and 35% at 300, 250 and 200 μM, respectively(P<0.000). Atranorin at 160-450 μM decreased cell proliferation at 72 h(P<0.000).Conclusions: Atranorin has cytotoxic, antiproliferative, apoptotic and cell migration inhibitory effects on SPC212 malignant mesothelioma cancer cells.
引文
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[4]Ristic S,Rankovic B,Kosanic M,Stanojkovic T,Stamenkovic S,Vasiljevic P,et al.Phytochemical study and antioxidant,antimicrobial and anticancer activities of Melanelia subaurifera and Melanelia fuliginosa lichens.J Food Sci Technol 2016;53(6):2804-2816.
[5]Molnár K,Farkas E.Current results on biological activities of lichen secondary metabolites:A review.Zeitschrift für Naturforschung C2010;65(3-4):157-173.
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[7]Studzinska-Sroka E,Galanty A,Bylka W.Atranorin-an interesting lichen secondary metabolite.Mini Rev Medchem 2017;17(17):1633-1645.
[8]Metinta?M.Asbest temas?na ba?l?plevral patolojiler ve mezotelyoma.Turkiye Klinikleri J Int Med Sci 2005;1(32):96-110.
[9]Metinta?M.Mezotelyoma’n?n Türkiye??in Epidemiyolojik?zellikleri,[Online]Available from:http://www.toraks.org.tr/uploadFiles/book/file/11112011162442-137141.pdf[Accessed on May 26,2019].
[10]Smith CW,Aptroot A,Coppins BJ,Fletcher A,Gilbert OL,James PW,et al.The lichens of Great Britain and Ireland.London,UK:British Lichen Society;2009.
[11]Sydow P.Die Flechten Deutschlands.Stuttgart:BoD-Books on Demand;2015,p.1244.
[12]Huneck S,Yoshimura I.Identification of lichen substances.In:Huneck S,Yoshimura I(eds.)Identification of lichen substances.Springer;1996,p.11-123.
[13]Orange A,James P,White FJ.Microchemical methods for the identification of lichens.London,UK:British Lichen Society;2001.
[14]Ke N,Wang X,Xu X,Abassi YA.The xCELLigence system for realtime and label-free monitoring of cell viability.In:Stoddart MJ(ed).Mammalian cell viability.Springer;2011,p.33-43.
[15]Galanty A,Koczurkiewicz P,Wnuk D,Paw M,Karnas E,Podolak I,et al.Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells.Toxicol In Vitro2017;40:161-169.
[16]Zhou R,Yang Y,Park SY,Nguyen TT,Seo YW,Lee KH,et al.The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis.Sci Rep 2017;7(1):8136.
[17]Solár P,Hr?kováG,Kopta?íkováL,VelebnyS,SolárováZ,Ba?kor M.Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro:Anticancer and hepatoprotective effects of atranorin in vivo.Chemico-Biol Interact2016;250:27-37.
[18]Russo A,Caggia S,Piovano M,Garbarino J,Cardile V.Effect of vicanicin and protolichesterinic acid on human prostate cancer cells:Role of Hsp70 protein.Chemico-Biol Interact 2012;195(1):1-10.
[19]de Melo MGD,de Souza Araújo AA,Serafini MR,Carvalho LF,Bezerra MS,Ramos CS,et al.Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents.Braz JPharm Sci 2011;47(4):861-872.
[20]Xu XF,Zhang TL,Jin S,Wang R,Xiao X,Zhang WD,et al.Ardipusilloside I induces apoptosis by regulating Bcl-2 family proteins in human mucoepidermoid carcinoma Mc3 cells.BMC Compl Alt Med2013;13:322.
[21]Ren MR,Hur JS,Kim JY,Park KW,Park SC,Seong CN,et al.Antiproliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells.Food Chem Toxicol 2009;47(9):2157-2162.
[22]Varol M,Tay T,Candan M,Turk A,Koparal AT.Evaluation of the sunscreen lichen substances usnic acid and atranorin.BioCell 2015;39(1):25-31.
[23]Yang Y,Park SY,Nguyen TT,Yu YH,Van Nguyen T,Sun EG,et al.Lichen secondary metabolite,physciosporin,inhibits lung cancer cell motility.Plos One 2015;10(9):e0137889.
[2]Gültekin S,?zyi?ito?lu G.Pseudevernia furfuracea(L.)Zopf Liken Türünün antibakteriyel aktivitesi ve antioksidan kapasitesinin ara?t?r?lmas?.Marmara Fen Bilimleri Dergisi 2018;30(2):210-216.
[3]Schinkovitz A,Le Pogam P,DerbréS,Roy-Vessieres E,Blanchard P,Thirumaran SL,et al.Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents.Fitoterapia 2018;131:182-188.
[4]Ristic S,Rankovic B,Kosanic M,Stanojkovic T,Stamenkovic S,Vasiljevic P,et al.Phytochemical study and antioxidant,antimicrobial and anticancer activities of Melanelia subaurifera and Melanelia fuliginosa lichens.J Food Sci Technol 2016;53(6):2804-2816.
[5]Molnár K,Farkas E.Current results on biological activities of lichen secondary metabolites:A review.Zeitschrift für Naturforschung C2010;65(3-4):157-173.
[6]Ba?korováM,Ba?kor M,Mike?J,Jend?elovskyR,Fedoro?ko P.Variable responses of different human cancer cells to the lichen compounds parietin,atranorin,usnic acid and gyrophoric acid.Toxicol In Vitro 2011;25(1):37-44.
[7]Studzinska-Sroka E,Galanty A,Bylka W.Atranorin-an interesting lichen secondary metabolite.Mini Rev Medchem 2017;17(17):1633-1645.
[8]Metinta?M.Asbest temas?na ba?l?plevral patolojiler ve mezotelyoma.Turkiye Klinikleri J Int Med Sci 2005;1(32):96-110.
[9]Metinta?M.Mezotelyoma’n?n Türkiye??in Epidemiyolojik?zellikleri,[Online]Available from:http://www.toraks.org.tr/uploadFiles/book/file/11112011162442-137141.pdf[Accessed on May 26,2019].
[10]Smith CW,Aptroot A,Coppins BJ,Fletcher A,Gilbert OL,James PW,et al.The lichens of Great Britain and Ireland.London,UK:British Lichen Society;2009.
[11]Sydow P.Die Flechten Deutschlands.Stuttgart:BoD-Books on Demand;2015,p.1244.
[12]Huneck S,Yoshimura I.Identification of lichen substances.In:Huneck S,Yoshimura I(eds.)Identification of lichen substances.Springer;1996,p.11-123.
[13]Orange A,James P,White FJ.Microchemical methods for the identification of lichens.London,UK:British Lichen Society;2001.
[14]Ke N,Wang X,Xu X,Abassi YA.The xCELLigence system for realtime and label-free monitoring of cell viability.In:Stoddart MJ(ed).Mammalian cell viability.Springer;2011,p.33-43.
[15]Galanty A,Koczurkiewicz P,Wnuk D,Paw M,Karnas E,Podolak I,et al.Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells.Toxicol In Vitro2017;40:161-169.
[16]Zhou R,Yang Y,Park SY,Nguyen TT,Seo YW,Lee KH,et al.The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis.Sci Rep 2017;7(1):8136.
[17]Solár P,Hr?kováG,Kopta?íkováL,VelebnyS,SolárováZ,Ba?kor M.Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro:Anticancer and hepatoprotective effects of atranorin in vivo.Chemico-Biol Interact2016;250:27-37.
[18]Russo A,Caggia S,Piovano M,Garbarino J,Cardile V.Effect of vicanicin and protolichesterinic acid on human prostate cancer cells:Role of Hsp70 protein.Chemico-Biol Interact 2012;195(1):1-10.
[19]de Melo MGD,de Souza Araújo AA,Serafini MR,Carvalho LF,Bezerra MS,Ramos CS,et al.Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents.Braz JPharm Sci 2011;47(4):861-872.
[20]Xu XF,Zhang TL,Jin S,Wang R,Xiao X,Zhang WD,et al.Ardipusilloside I induces apoptosis by regulating Bcl-2 family proteins in human mucoepidermoid carcinoma Mc3 cells.BMC Compl Alt Med2013;13:322.
[21]Ren MR,Hur JS,Kim JY,Park KW,Park SC,Seong CN,et al.Antiproliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells.Food Chem Toxicol 2009;47(9):2157-2162.
[22]Varol M,Tay T,Candan M,Turk A,Koparal AT.Evaluation of the sunscreen lichen substances usnic acid and atranorin.BioCell 2015;39(1):25-31.
[23]Yang Y,Park SY,Nguyen TT,Yu YH,Van Nguyen T,Sun EG,et al.Lichen secondary metabolite,physciosporin,inhibits lung cancer cell motility.Plos One 2015;10(9):e0137889.