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Erschienen in: European Archives of Oto-Rhino-Laryngology 6/2014

01.06.2014 | Laryngology

Luteolin induces apoptosis by activating Fas signaling pathway at the receptor level in laryngeal squamous cell line Hep-2 cells

verfasst von: Hui Zhang, Xiuguo Li, Yuanyuan Zhang, Xinyong Luan

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 6/2014

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Abstract

Luteolin, a naturally occurring flavonoid, possesses anti-cancer activities against several human cancers, but the exact molecular and biochemical mechanisms of above findings are not very clear, and its activity against head and neck squamous cell carcinoma (HNSCC) is seldom mentioned. In this study, we investigated luteolin against human laryngeal squamous cell line Hep-2 cells, using MTT assay, flow cytometry, Western blot and reverse transcriptase–polymerase chain reaction (RT-PCR) analysis. Luteolin inhibited Hep-2 cells proliferation at the inhibitive concentrations of 50 % (IC50) near to 50 μM and induced the apoptosis in Hep-2 cells through caspase-3 and caspase-8 activation. Up-regulation of Fas and down-regulation of long form cellular FLICE-like inhibitory protein (c-FLIPL) protein were also involved after luteolin treatment at both protein and mRNA levels. Luteolin could not only inhibit cell proliferation but also induce apoptosis by activating the Fas signaling pathway at the receptor level in laryngeal squamous cell line Hep-2 cells.
Literatur
1.
Zurück zum Zitat Yang RY, Lin S, Kuo G (2008) Content and distribution of flavonoids among 91 edible plant species. Asia Pac J Clin Nutr. 17(Suppl 1):275–279PubMed Yang RY, Lin S, Kuo G (2008) Content and distribution of flavonoids among 91 edible plant species. Asia Pac J Clin Nutr. 17(Suppl 1):275–279PubMed
2.
Zurück zum Zitat Imai M, Kikuchi H, Denda T et al (2009) Cytotoxic effects of flavonoids against a human colon cancer derived cell line, COLO 201: a potential natural anti-cancer substance. Cancer Lett 276:74–80PubMedCrossRef Imai M, Kikuchi H, Denda T et al (2009) Cytotoxic effects of flavonoids against a human colon cancer derived cell line, COLO 201: a potential natural anti-cancer substance. Cancer Lett 276:74–80PubMedCrossRef
3.
Zurück zum Zitat Terao J, Kawai Y, Murota K (2008) Vegetable flavonoids and cardiovascular disease. Asia Pac J Clin Nutr 17(Suppl 1):291–293PubMed Terao J, Kawai Y, Murota K (2008) Vegetable flavonoids and cardiovascular disease. Asia Pac J Clin Nutr 17(Suppl 1):291–293PubMed
4.
Zurück zum Zitat Simons R, Gruppen H, Bovee TF et al (2012) Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs). Food Funct 3(8):810–827PubMedCrossRef Simons R, Gruppen H, Bovee TF et al (2012) Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs). Food Funct 3(8):810–827PubMedCrossRef
5.
Zurück zum Zitat Meeran SM, Vaid M, Punathil T, Katiyar SK (2009) Dietary grape seed proanthocyanidins inhibit 12-O-tetradecanoyl phorbol-13-acetate-caused skin tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated mouse skin, which is associated with the inhibition of inflammatory responses. Carcinogenesis 30(3):520–528PubMedCrossRef Meeran SM, Vaid M, Punathil T, Katiyar SK (2009) Dietary grape seed proanthocyanidins inhibit 12-O-tetradecanoyl phorbol-13-acetate-caused skin tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated mouse skin, which is associated with the inhibition of inflammatory responses. Carcinogenesis 30(3):520–528PubMedCrossRef
6.
7.
Zurück zum Zitat Chow AK, Ng L, Sing Li H et al (2012) Anti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma. Curr Cancer Drug Targets 12(9):1233–1243PubMed Chow AK, Ng L, Sing Li H et al (2012) Anti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma. Curr Cancer Drug Targets 12(9):1233–1243PubMed
8.
Zurück zum Zitat Lange F, Brandt B, Tiedge M et al (2009) Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence for a connection between death-receptor and mitochondrial pathways in human Jurkat T lymphocytes. Histochem Cell Biol 132(2):211–223PubMedCrossRef Lange F, Brandt B, Tiedge M et al (2009) Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence for a connection between death-receptor and mitochondrial pathways in human Jurkat T lymphocytes. Histochem Cell Biol 132(2):211–223PubMedCrossRef
9.
Zurück zum Zitat Zhang M, Lee SJ, An C et al (2011) Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis. Free Radical Biol Med 50(10):1252–1262CrossRef Zhang M, Lee SJ, An C et al (2011) Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis. Free Radical Biol Med 50(10):1252–1262CrossRef
10.
Zurück zum Zitat Xu B, Xu Z, Xia T et al (2011) Effects of the Fas/Fas-L pathway on fluoride-induced apoptosis in SH-SY5Y cells. Environ Toxicol 26(1):86–92PubMedCrossRef Xu B, Xu Z, Xia T et al (2011) Effects of the Fas/Fas-L pathway on fluoride-induced apoptosis in SH-SY5Y cells. Environ Toxicol 26(1):86–92PubMedCrossRef
11.
Zurück zum Zitat Konstantakou EG, Voutsinas GE, Karkoulis PK et al (2009) Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses. Int J Oncol 35(2):401–416PubMed Konstantakou EG, Voutsinas GE, Karkoulis PK et al (2009) Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses. Int J Oncol 35(2):401–416PubMed
12.
Zurück zum Zitat Sproll KC, Ballo H, Hoffmann TK et al (2009) Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)? Oral Oncol 45(1):69–84PubMedCrossRef Sproll KC, Ballo H, Hoffmann TK et al (2009) Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)? Oral Oncol 45(1):69–84PubMedCrossRef
13.
Zurück zum Zitat Subramaniam K, Hirpara JL, Tucker-Kellogg L et al (2013) FLIP: a flop for execution signals. Cancer Lett 332(2):151–155PubMedCrossRef Subramaniam K, Hirpara JL, Tucker-Kellogg L et al (2013) FLIP: a flop for execution signals. Cancer Lett 332(2):151–155PubMedCrossRef
14.
Zurück zum Zitat Hotta T, Suzuki H, Nagai S et al (2003) Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. J Orthop Res 21(5):949–957PubMedCrossRef Hotta T, Suzuki H, Nagai S et al (2003) Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. J Orthop Res 21(5):949–957PubMedCrossRef
15.
Zurück zum Zitat Grobner S, Adkins I, Schulz S et al (2007) Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells. Apoptosis 12(10):1813–1825PubMedCrossRef Grobner S, Adkins I, Schulz S et al (2007) Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells. Apoptosis 12(10):1813–1825PubMedCrossRef
16.
Zurück zum Zitat Rasper DM, Vaillancourt JP, Hadano S et al (1998) Cell death attenuation by ‘Usurpin’, a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell Death Differ 5(4):271–288PubMedCrossRef Rasper DM, Vaillancourt JP, Hadano S et al (1998) Cell death attenuation by ‘Usurpin’, a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell Death Differ 5(4):271–288PubMedCrossRef
17.
Zurück zum Zitat Lim JH, Park JW, Choi KS et al (2009) Rottlerin induces apoptosis via death receptor 5 (DR5) up-regulation through CHOP-dependent and PKC delta-independent mechanism in human malignant tumor cells. Carcinogenesis 30(5):729–736PubMedCrossRef Lim JH, Park JW, Choi KS et al (2009) Rottlerin induces apoptosis via death receptor 5 (DR5) up-regulation through CHOP-dependent and PKC delta-independent mechanism in human malignant tumor cells. Carcinogenesis 30(5):729–736PubMedCrossRef
18.
Zurück zum Zitat Subramaniam A, Shanmugam MK, Perumal E et al (2013) Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochimica biophysica acta 1835:46–60 Subramaniam A, Shanmugam MK, Perumal E et al (2013) Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochimica biophysica acta 1835:46–60
19.
Zurück zum Zitat Wang L, Azad N, Kongkaneramit L et al (2008) The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol 180(5):3072–3080PubMedCentralPubMedCrossRef Wang L, Azad N, Kongkaneramit L et al (2008) The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol 180(5):3072–3080PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Bhattacharya S, Haldar PK (2012) Chemopreventive property of Trichosanthes dioica root against 3-methylcholanthrene-induced carcinogenesis in albino mice. J Environ Pathol Toxicol Oncol 31(2):109–119PubMedCrossRef Bhattacharya S, Haldar PK (2012) Chemopreventive property of Trichosanthes dioica root against 3-methylcholanthrene-induced carcinogenesis in albino mice. J Environ Pathol Toxicol Oncol 31(2):109–119PubMedCrossRef
21.
Zurück zum Zitat Kaulfuss S, Burfeind P, Gaedcke J, Scharf JG (2009) Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis. Mol Cancer Ther 8(4):821–833PubMedCrossRef Kaulfuss S, Burfeind P, Gaedcke J, Scharf JG (2009) Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis. Mol Cancer Ther 8(4):821–833PubMedCrossRef
22.
Zurück zum Zitat Kim BM, Choi YJ, Han Y et al (2009) N, N-dimethyl phytosphingosine induces caspase-8-dependent cytochrome c release and apoptosis through ROS generation in human leukemia cells. Toxicol Appl Pharmacol 239(1):87–97PubMedCrossRef Kim BM, Choi YJ, Han Y et al (2009) N, N-dimethyl phytosphingosine induces caspase-8-dependent cytochrome c release and apoptosis through ROS generation in human leukemia cells. Toxicol Appl Pharmacol 239(1):87–97PubMedCrossRef
23.
Zurück zum Zitat Kim MJ, Choi SY, Park IC et al (2008) Opposing roles of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in the cellular response to ionizing radiation in human cervical cancer cells. Mol Cancer Res 6(11):1718–1731PubMedCrossRef Kim MJ, Choi SY, Park IC et al (2008) Opposing roles of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in the cellular response to ionizing radiation in human cervical cancer cells. Mol Cancer Res 6(11):1718–1731PubMedCrossRef
24.
Zurück zum Zitat Markaverich BM, Vijjeswarapu M, Shoulars K, Rodriguez M (2010) Luteolin and gefitinib regulation of EGF signaling pathway and cell cycle pathway genes in PC-3 human prostate cancer cells. J Steroid Biochem Mol Biol 122(4):219–231PubMedCentralPubMedCrossRef Markaverich BM, Vijjeswarapu M, Shoulars K, Rodriguez M (2010) Luteolin and gefitinib regulation of EGF signaling pathway and cell cycle pathway genes in PC-3 human prostate cancer cells. J Steroid Biochem Mol Biol 122(4):219–231PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Roy A, Das BB, Ganguly A et al (2008) An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3′-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme. Biochem J 409(2):611–622PubMedCrossRef Roy A, Das BB, Ganguly A et al (2008) An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3′-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme. Biochem J 409(2):611–622PubMedCrossRef
26.
Zurück zum Zitat Brumatti G, Yon M, Castro FA et al (2008) Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide. Exp Cell Res 314(3):554–563PubMedCrossRef Brumatti G, Yon M, Castro FA et al (2008) Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of cycloheximide. Exp Cell Res 314(3):554–563PubMedCrossRef
27.
Zurück zum Zitat Pforr C, Neumann L, Eils R et al (2011) Understanding life and death at CD95. Adv Exp Med Biol 691:151–161PubMedCrossRef Pforr C, Neumann L, Eils R et al (2011) Understanding life and death at CD95. Adv Exp Med Biol 691:151–161PubMedCrossRef
28.
Zurück zum Zitat Iwase M, Takaoka S, Uchida M et al (2008) Epidermal growth factor receptor inhibitors enhance susceptibility to Fas-mediated apoptosis in oral squamous cell carcinoma cells. Oral Oncol 44(4):361–368PubMedCrossRef Iwase M, Takaoka S, Uchida M et al (2008) Epidermal growth factor receptor inhibitors enhance susceptibility to Fas-mediated apoptosis in oral squamous cell carcinoma cells. Oral Oncol 44(4):361–368PubMedCrossRef
29.
Zurück zum Zitat Safa AR, Day TW, Wu CH (2008) Cellular FLICE-like inhibitory protein (C-FLIP): a novel target for cancer therapy. Curr Cancer Drug Targets 8(1):37–46PubMedCrossRef Safa AR, Day TW, Wu CH (2008) Cellular FLICE-like inhibitory protein (C-FLIP): a novel target for cancer therapy. Curr Cancer Drug Targets 8(1):37–46PubMedCrossRef
30.
Zurück zum Zitat Diessenbacher P, Hupe M, Sprick MR et al (2008) NF-kappa B inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2. J Invest Dermatol 128(5):1134–1147PubMedCrossRef Diessenbacher P, Hupe M, Sprick MR et al (2008) NF-kappa B inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2. J Invest Dermatol 128(5):1134–1147PubMedCrossRef
31.
Zurück zum Zitat Fulda S (2013) Targeting c-FLICE-like inhibitory protein (CFLAR) in cancer. Expert Opin Ther Targets 17(2):195–201PubMedCrossRef Fulda S (2013) Targeting c-FLICE-like inhibitory protein (CFLAR) in cancer. Expert Opin Ther Targets 17(2):195–201PubMedCrossRef
32.
Zurück zum Zitat Kim MO, Kim MH, Lee SH et al (2009) 5′-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2 +)/PKC, cAMP signaling pathways in mouse embryonic stem cells. J Cell Physiol 219(3):752–759PubMedCrossRef Kim MO, Kim MH, Lee SH et al (2009) 5′-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2 +)/PKC, cAMP signaling pathways in mouse embryonic stem cells. J Cell Physiol 219(3):752–759PubMedCrossRef
33.
Zurück zum Zitat Day TW, Najafi F, Wu CH, Safa AR (2006) Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis. Biochem Pharmacol 71(11):1551–1561PubMedCrossRef Day TW, Najafi F, Wu CH, Safa AR (2006) Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis. Biochem Pharmacol 71(11):1551–1561PubMedCrossRef
34.
Zurück zum Zitat Llobet D, Eritja N, Encinas M et al (2008) CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells. Oncogene 27(18):2513–2524PubMedCrossRef Llobet D, Eritja N, Encinas M et al (2008) CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells. Oncogene 27(18):2513–2524PubMedCrossRef
35.
Zurück zum Zitat Kreuz S, Siegmund D, Scheurich P, Wajant H (2001) NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol Cell Biol 21(12):3964–3973PubMedCentralPubMedCrossRef Kreuz S, Siegmund D, Scheurich P, Wajant H (2001) NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol Cell Biol 21(12):3964–3973PubMedCentralPubMedCrossRef
36.
Zurück zum Zitat Panka DJ, Mano T, Suhara T et al (2001) Phosphatidylinositol 3-kinase/Akt activity regulates c-FLIP expression in tumor cells. J Biol Chem 276(10):6893–6896PubMedCrossRef Panka DJ, Mano T, Suhara T et al (2001) Phosphatidylinositol 3-kinase/Akt activity regulates c-FLIP expression in tumor cells. J Biol Chem 276(10):6893–6896PubMedCrossRef
37.
Zurück zum Zitat Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–671PubMed Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–671PubMed
38.
Zurück zum Zitat Horinaka M, Yoshida T, Shiraishi T et al (2005) Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 24(48):7180–7189PubMedCrossRef Horinaka M, Yoshida T, Shiraishi T et al (2005) Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 24(48):7180–7189PubMedCrossRef
39.
Zurück zum Zitat Fu J, Chen D, Zhao B et al (2012) Luteolin induces carcinoma cell apoptosis through binding Hsp90 to suppress constitutive activation of STAT3. PLoS One 7(11):e49194PubMedCentralPubMedCrossRef Fu J, Chen D, Zhao B et al (2012) Luteolin induces carcinoma cell apoptosis through binding Hsp90 to suppress constitutive activation of STAT3. PLoS One 7(11):e49194PubMedCentralPubMedCrossRef
40.
Zurück zum Zitat Haag C, Stadel D, Zhou S et al (2011) Identification of c-FLIP(L) and c-FLIP(S) as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells. Gut 60(2):225–237PubMedCrossRef Haag C, Stadel D, Zhou S et al (2011) Identification of c-FLIP(L) and c-FLIP(S) as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells. Gut 60(2):225–237PubMedCrossRef
41.
Zurück zum Zitat Kinoshita H, Yoshikawa H, Shiiki K et al (2000) Cisplatin (CDDP) sensitizes human osteosarcoma cell to Fas/CD95-mediated apoptosis by down-regulating FLIP-L expression. Int J Cancer 88(6):986–991PubMedCrossRef Kinoshita H, Yoshikawa H, Shiiki K et al (2000) Cisplatin (CDDP) sensitizes human osteosarcoma cell to Fas/CD95-mediated apoptosis by down-regulating FLIP-L expression. Int J Cancer 88(6):986–991PubMedCrossRef
42.
Zurück zum Zitat Mendenhall WM, Parsons JT, Stringer SP et al (1988) T1-T2 vocal cord carcinoma: a basis for comparing the results of radiotherapy and surgery[J]. Head Neck Surg 10(6):373–377PubMedCrossRef Mendenhall WM, Parsons JT, Stringer SP et al (1988) T1-T2 vocal cord carcinoma: a basis for comparing the results of radiotherapy and surgery[J]. Head Neck Surg 10(6):373–377PubMedCrossRef
43.
Zurück zum Zitat Persky MS, Lagmay VM, Cooper J et al (2000) Curative radiotherapy for anterior commissure laryngeal carcinoma. Ann Otol Rhinol Laryngol 109(2):156–159PubMed Persky MS, Lagmay VM, Cooper J et al (2000) Curative radiotherapy for anterior commissure laryngeal carcinoma. Ann Otol Rhinol Laryngol 109(2):156–159PubMed
Metadaten
Titel
Luteolin induces apoptosis by activating Fas signaling pathway at the receptor level in laryngeal squamous cell line Hep-2 cells
verfasst von
Hui Zhang
Xiuguo Li
Yuanyuan Zhang
Xinyong Luan
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 6/2014
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-014-2903-z

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